Academia.eduAcademia.edu

Outline

Inmune response of the eye copia

Abstract
sparkles

AI

The study investigates the complex immune responses occurring within the eye, focusing on the mechanisms of innate and adaptive immunity, immune privilege, and the role of various cell types such as antigen-presenting cells and T cells. It examines how these immune mechanisms affect pathologies like autoimmune diseases and responses to infections, suggesting that the ocular environment has unique properties that contribute to its immune tolerance. Implications for future research and potential therapeutic targets are also discussed.

References (1,547)

  1. Heeger PS, Lalli PN, Lin F , et al: Decay-accelerating factor modulates induction of T cell immu- nity. J Exp Med 2005;201:1523-1530.
  2. Staats HF , Jackson RJ, Marinaro M, et al: Mucosal immunity to infection with implications for vaccine development. Curr Opin Immunol 1994;6:572-583.
  3. Garside P, Millington O, Smith KM: The anatomy of mucosal immune responses. Ann NY Acad Sci 2004;1029:9-15.
  4. Mestecky J: The common mucosal immune system and current strategies for induction of immune responses in external secretions. J Clin Immunol 1987;7:265-276.
  5. Sullivan DA: Immunology of the lacrimal gland and tear film. Dev Ophthalmol 1999;30:39-53.
  6. Mazanec MB, Nedrud JG, Kaetzel CS, Lamm ME: A three-tiered view of the role of IgA in mucosal defense. Immunol Today 1993;14:430-435.
  7. Niederkorn JY: The role of the innate and adaptive immune responses in Acanthamoeba keratitis. Arch Immunol Ther Exp (Warsz) 2002;50:53-59.
  8. Dubois B, Goubier A, Joubert G, Kaiserlian D: Oral tolerance and regulation of mucosal immu- nity. Cell Mol Life Sci 2005;62:1322-1332.
  9. 9 Garside P , Mowat AM: Mechanisms of oral tolerance. Crit Rev Immunol 1997;17:119-137.
  10. Mowat AM, Parker LA, Beacock-Sharp H, Millington OR, Chirdo F: Oral tolerance: overview and historical perspectives. Ann NY Acad Sci 2004;1029:1-8.
  11. Wu HY, Weiner HL: Oral tolerance. Immunol Res 2003;28:265-284.
  12. Wells HG: Studies on the chemistry of anaphylaxis. III. Experiments with isolated proteins, espe- cially those of hen's egg. J Infect Dis 1911;9:147-171.
  13. Barker CF, Billingham RE: Immunologically privileged sites. Adv Immunol 1977;25:1-54.
  14. Harling-Berg C, Knopf PM, Merriam J, Cserr HF: Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid. J Neuroimmunol 1989;25:185-193.
  15. Yamada S, DePasquale M, Patlak CS, Cserr HF: Albumin outflow into deep cervical lymph from different regions of rabbit brain. Am J Physiol 1991;261:H1197-H1204.
  16. Harling-Berg CJ, Knopf PM, Cserr HF: Myelin basic protein infused into cerebrospinal fluid sup- presses experimental autoimmune encephalomyelitis. J Neuroimmunol 1991;35:45-51.
  17. Wenkel H, Streilein JW, Young MJ: Systemic immune deviation in the brain that does not depend on the integrity of the blood-brain barrier. J Immunol 2000;164:5125-5131.
  18. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189-1192.
  19. Choi C, Benveniste EN: Fas ligand/Fas system in the brain: regulator of immune and apoptotic responses. Brain Res Brain Res Rev 2004;44:65-81.
  20. Sata M, Suhara T, Walsh K: Vascular endothelial cells and smooth muscle cells differ in expression of Fas and Fas ligand and in sensitivity to Fas ligand-induced cell death: implications for vascular disease and therapy. Arterioscler Thromb Vasc Biol 2000;20:309-316.
  21. Walsh K, Sata M: Is extravasation a Fas-regulated process? Mol Med Today 1999;5:61-67.
  22. Moffett-King A: Natural killer cells and pregnancy. Nat Rev Immunol 2002;2:656-663.
  23. Ljunggren HG, Ohlen C, Hoglund P, Franksson L, Karre K: The RMA-S lymphoma mutant: con- sequences of a peptide loading defect on immunological recognition and graft rejection. Int J Cancer Suppl 1991;6:38-44.
  24. Ishitani A, Geraghty DE: Alternative splicing of HLA-G transcripts yields proteins with primary structures resembling both class I and class II antigens. Proc Natl Acad Sci USA 1992;89: 3947-3951.
  25. Kovats S, Main EK, Librach C, et al: A class I antigen, HLA-G, expressed in human trophoblasts. Science 1990;248:220-223.
  26. Rouas-Freiss N, Goncalves RM, Menier C, Dausset J, Carosella ED: Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci USA 1997;94:11520-11525.
  27. Rouas-Freiss N, Khalil-Daher I, Marchal-Bras Goncalves R, et al: Role of HLA-G in maternal- fetal immune tolerance. Transplant Proc 1999;31:724-725.
  28. Rouas-Freiss N, Khalil-Daher I, Riteau B, et al: The immunotolerance role of HLA-G. Semin Cancer Biol 1999;9:3-12.
  29. Lee N, Llano M, Carretero M, et al: HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc Natl Acad Sci USA 1998;95:5199-5204.
  30. Niederkorn JY: Immune privilege of the eye and fetus: parallel universes? Transplantation 2005;80:1139-1144.
  31. Robertson SA, Ingman WV, O'Leary S, Sharkey DJ, Tremellen KP: Transforming growth factor beta -a mediator of immune deviation in seminal plasma. J Reprod Immunol 2002;57: 109-128.
  32. Tremellen KP, Seamark RF, Robertson SA: Seminal transforming growth factor ␤ 1 stimulates granulocyte-macrophage colony-stimulating factor production and inflammatory cell recruitment in the murine uterus. Biol Reprod 1998;58:1217-1225.
  33. James E, Chai JG, Dewchand H, et al: Multiparity induces priming to male-specific minor histo- compatibility antigen, HY, in mice and humans. Blood 2003;102:388-393.
  34. Lengerova A, Vojtiskova M: Prolonged survival of syngeneic male skin grafts in parous C57B1 mice. Folia Biol (Praha) 1963;9:72-74.
  35. Robertson SA, Mau VJ, Hudson SN, Tremellen KP: Cytokine-leukocyte networks and the estab- lishment of pregnancy. Am J Reprod Immunol 1997;37:438-442.
  36. Tafuri A, Alferink J, Moller P, Hammerling GJ, Arnold B: T cell awareness of paternal alloantigens during pregnancy. Science 1995;270:630-633.
  37. Tremellen KP, Valbuena D, Landeras J, et al: The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000;15:2653-2658.
  38. Aluvihare VR, Kallikourdis M, Betz AG: Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 2004;5:266-271.
  39. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT: Normal human pregnancy is asso- ciated with an elevation in the immune suppressive CD25ϩ CD4ϩ regulatory T-cell subset. Immunology 2004;112:38-43.
  40. Medawar PB: Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol 1948;29:58-69.
  41. Billingham RE, Boswell T: Studies on the problem of corneal homografts. Proc R Soc Lond B Biol Sci 1953;141:392-406.
  42. Kaplan HJ, Stevens TR: A reconsideration of immunological privilege within the anterior chamber of the eye. Transplantation 1975;19:203-209.
  43. Kaplan HJ, Streilein JW: Immune response to immunization via the anterior chamber of the eye. I. F1-lymphocyte-induced immune deviation. J Immunol 1977;118:809-814.
  44. Kaplan HJ, Streilein JW: Immune response to immunization via the anterior chamber of the eye. II. An analysis of F1 lymphocyte-induced immune deviation. J Immunol 1978;120:689-693.
  45. Niederkorn J, Streilein JW, Shadduck JA: Deviant immune responses to allogeneic tumors injected intracamerally and subcutaneously in mice. Invest Ophthalmol Vis Sci 1981;20:355-363.
  46. Niederkorn JY: Immune privilege in the anterior chamber of the eye. Crit Rev Immunol 2002;22:13-46.
  47. Streilein JW, Niederkorn JY, Shadduck JA: Systemic immune unresponsiveness induced in adult mice by anterior chamber presentation of minor histocompatibility antigens. J Exp Med 1980;152: 1121-1125.
  48. Streilein JW, Niederkorn JY: Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J Exp Med 1981;153:1058-1067.
  49. Jiang LQ, Jorquera M, Streilein JW: Subretinal space and vitreous cavity as immunologically priv- ileged sites for retinal allografts. Invest Ophthalmol Vis Sci 1993;34:3347-3354.
  50. Wenkel H, Chen PW, Ksander BR, Streilein JW: Immune privilege is extended, then withdrawn, from allogeneic tumor cell grafts placed in the subretinal space. Invest Ophthalmol Vis Sci 1999;40:3202-3208.
  51. Junghans BM, Wadley RB, Crewther SG, Crewther DP: X-ray elemental analysis differentiates blood vessels and lymphatic vessels in the chick choroid. Aust NZ J Ophthalmol 1999;27: 244-246.
  52. Liang H, Crewther SG, Crewther DP, Junghans BM: Structural and elemental evidence for edema in the retina, retinal pigment epithelium, and choroid during recovery from experimentally induced myopia. Invest Ophthalmol Vis Sci 2004;45:2463-2474.
  53. Boonman ZF, van Mierlo GJ, Fransen MF, et al: Intraocular tumor antigen drains specifically to submandibular lymph nodes, resulting in an abortive cytotoxic T cell reaction. J Immunol 2004;172:1567-1574.
  54. Camelo S, Kezic J, Shanley A, Rigby P, McMenamin PG: Antigen from the anterior chamber of the eye travels in a soluble form to secondary lymphoid organs via lymphatic and vascular routes. Invest Ophthalmol Vis Sci 2006;47:1039-1046.
  55. Camelo S, Shanley A, Voon AS, McMenamin PG: The distribution of antigen in lymphoid tissues following its injection into the anterior chamber of the rat eye. J Immunol 2004;172:5388-5395.
  56. Egan RM, Yorkey C, Black R, et al: Peptide-specific T cell clonal expansion in vivo following immunization in the eye, an immune-privileged site. J Immunol 1996;157:2262-2271.
  57. Liu Y, Hamrah P, Zhang Q, Taylor AW, Dana MR: Draining lymph nodes of corneal transplant hosts exhibit evidence for donor major histocompatibility complex (MHC) class II-positive den- dritic cells derived from MHC class II-negative grafts. J Exp Med 2002;195:259-268.
  58. Niederkorn JY, Lynch MG: Reconsidering the immunologic privilege and lymphatic drainage of the anterior chamber of the eye. Transplant Proc 1989;21:259-260.
  59. Niederkorn JY, Streilein JW: Alloantigens placed into the anterior chamber of the eye induce spe- cific suppression of delayed-type hypersensitivity but normal cytotoxic T lymphocyte and helper T lymphocyte responses. J Immunol 1983;131:2670-2674.
  60. Niederkorn JY: Immunology and immunomodulation of corneal transplantation. Int Rev Immunol 2002;21:173-196.
  61. Abi-Hanna D, Wakefield D, Watkins S: HLA antigens in ocular tissues. I. In vivo expression in human eyes. Transplantation 1988;45:610-613.
  62. Wang HM, Kaplan HJ, Chan WC, Johnson M: The distribution and ontogeny of MHC antigens in murine ocular tissue. Invest Ophthalmol Vis Sci 1987;28:1383-1389.
  63. Hamrah P, Liu Y, Zhang Q, Dana MR: The corneal stroma is endowed with a significant number of resident dendritic cells. Invest Ophthalmol Vis Sci 2003;44:581-589.
  64. Lee RS, Grusby MJ, Glimcher LH, Winn HJ, Auchincloss H Jr: Indirect recognition by helper cells can induce donor-specific cytotoxic T lymphocytes in vivo. J Exp Med 1994;179:865-872.
  65. Shoskes DA, Wood KJ: Indirect presentation of MHC antigens in transplantation. Immunol Today 1994;15:32-38.
  66. Streilein JW, Toews GB, Bergstresser PR: Corneal allografts fail to express Ia antigens. Nature 1979;282:326-327.
  67. Cursiefen C, Chen L, Dana MR, Streilein JW: Corneal lymphangiogenesis: evidence, mecha- nisms, and implications for corneal transplant immunology. Cornea 2003;22:273-281.
  68. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:879-889.
  69. Hegde S, Beauregard C, Mayhew E, Niederkorn JY: CD4ϩ T-cell-mediated mechanisms of corneal allograft rejection: role of Fas-induced apoptosis. Transplantation 2005;79:23-31.
  70. Hegde S, Niederkorn JY: The role of cytotoxic T lymphocytes in corneal allograft rejection. Invest Ophthalmol Vis Sci 2000;41:3341-3347.
  71. Niederkorn JY: The immunology of corneal transplantation. Dev Ophthalmol 1999;30:129-140.
  72. Hori J, Streilein JW: Role of recipient epithelium in promoting survival of orthotopic corneal allo- grafts in mice. Invest Ophthalmol Vis Sci 2001;42:720-726.
  73. Jiang LQ, Streilein JW: Immune privilege extended to allogeneic tumor cells in the vitreous cav- ity. Invest Ophthalmol Vis Sci 1991;32:224-228.
  74. Wenkel H, Streilein JW: Analysis of immune deviation elicited by antigens injected into the sub- retinal space. Invest Ophthalmol Vis Sci 1998;39:1823-1834.
  75. Ksander BR, Geer DC, Chen PW, et al: Uveal melanomas contain antigenically specific and non- specific infiltrating lymphocytes. Curr Eye Res 1998;17:165-173.
  76. Wilbanks GA, Streilein JW: Distinctive humoral immune responses following anterior chamber and intravenous administration of soluble antigen. Evidence for active suppression of IgG2-secreting B lymphocytes. Immunology 1990;71:566-572.
  77. Lin HH, Faunce DE, Stacey M, et al: The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. J Exp Med 2005;201:1615-1625.
  78. Ferguson TA, Herndon JM: The immune response and the eye: the ACAID inducing signal is dependent on the nature of the antigen. Invest Ophthalmol Vis Sci 1994;35:3085-3093.
  79. Ferguson TA, Kaplan HJ: The immune response and the eye. I. The effects of monoclonal antibod- ies to T suppressor factors in anterior chamber-associated immune deviation (ACAID). J Immunol 1987;139:346-351.
  80. Waldrep JC, Kaplan HJ: Anterior chamber-associated immune deviation induced by TNP-splenocytes (TNP-ACAID). II. Suppressor T-cell networks. Invest Ophthalmol Vis Sci 1983;24:1339-1345.
  81. Skelsey ME, Mayhew E, Niederkorn JY: CD25ϩ, interleukin-10-producing CD4ϩ T cells are required for suppressor cell production and immune privilege in the anterior chamber of the eye. Immunology 2003;110:18-29.
  82. Stein-Streilein J, Streilein JW: Anterior chamber associated immune deviation (ACAID): regulation, biological relevance, and implications for therapy. Int Rev Immunol 2002;21: 123-152.
  83. Streilein JW, Masli S, Takeuchi M, Kezuka T: The eye's view of antigen presentation. Hum Immunol 2002;63:435-443.
  84. Taylor AW, Yee DG: Somatostatin is an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 2003;44:2644-2649.
  85. Namba K, Kitaichi N, Nishida T, Taylor AW: Induction of regulatory T cells by the immunomodu- lating cytokines ␣-melanocyte-stimulating hormone and transforming growth factor-␤ 2 . J Leukoc Biol 2002;72:946-952.
  86. Taylor AW, Streilein JW, Cousins SW: Identification of ␣-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor. Curr Eye Res 1992;11:1199-1206.
  87. Taylor AW, Yee DG, Streilein JW: Suppression of nitric oxide generated by inflammatory macrophages by calcitonin gene-related peptide in aqueous humor. Invest Ophthalmol Vis Sci 1998;39:1372-1378.
  88. Apte RS, Sinha D, Mayhew E, Wistow GJ, Niederkorn JY: Cutting edge: role of macrophage migration inhibitory factor in inhibiting NK cell activity and preserving immune privilege. J Immunol 1998;160:5693-5696.
  89. Gregory MS, Repp AC, Holhbaum AM, et al: Membrane Fas ligand activates innate immunity and terminates ocular immune privilege. J Immunol 2002;169:2727-2735.
  90. Taylor AW: Ocular immunosuppressive microenvironment; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 72-89.
  91. Goslings WR, Prodeus AP, Streilein JW, et al: A small molecular weight factor in aqueous humor acts on C1q to prevent antibody-dependent complement activation. Invest Ophthalmol Vis Sci 1998;39:989-995.
  92. Sohn JH, Bora PS, Suk HJ, et al: Tolerance is dependent on complement C3 fragment iC3b bind- ing to antigen-presenting cells. Nat Med 2003;9:206-212.
  93. Bora NS, Gobleman CL, Atkinson JP, Pepose JS, Kaplan HJ: Differential expression of the com- plement regulatory proteins in the human eye. Invest Ophthalmol Vis Sci 1993;34:3579-3584.
  94. Lass JH, Walter EI, Burris TE, et al: Expression of two molecular forms of the complement decay- accelerating factor in the eye and lacrimal gland. Invest Ophthalmol Vis Sci 1990;31:1136-1148.
  95. Sohn JH, Kaplan HJ, Suk HJ, Bora PS, Bora NS: Complement regulatory activity of normal human intraocular fluid is mediated by MCP, DAF, and CD59. Invest Ophthalmol Vis Sci 2000;41:4195-4202.
  96. Sohn JH, Kaplan HJ, Suk HJ, Bora PS, Bora NS: Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins. Invest Ophthalmol Vis Sci 2000;41:3492-3502.
  97. Yoshida M, Takeuchi M, Streilein JW: Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 1. Inhibition of T-cell activation in vitro by direct cell-to-cell contact. Invest Ophthalmol Vis Sci 2000;41:811-821.
  98. Lee HO, Herndon JM, Barreiro R, Griffith TS, Ferguson TA: TRAIL: a mechanism of tumor sur- veillance in an immune privileged site. J Immunol 2002;169:4739-4744.
  99. Wang S, Boonman ZF, Li HC, et al: Role of TRAIL and IFN-gamma in CD4ϩ T cell-dependent tumor rejection in the anterior chamber of the eye. J Immunol 2003;171:2789-2796.
  100. Mo JS, Streilein JW: Immune privilege persists in eyes with extreme inflammation induced by intravitreal LPS. Eur J Immunol 2001;31:3806-3815.
  101. Ohta K, Wiggert B, Yamagami S, Taylor AW, Streilein JW: Analysis of immunomodulatory activi- ties of aqueous humor from eyes of mice with experimental autoimmune uveitis. J Immunol 2000;164:1185-1192.
  102. Ohta K, Yamagami S, Taylor AW, Streilein JW: IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 2000;41:2591-2599.
  103. Streilein JW, Ohta K, Mo JS, Taylor AW: Ocular immune privilege and the impact of intraocular inflammation. DNA Cell Biol 2002;21:453-459.
  104. van Dooremaal JC: Die Entwicklung der in fremden Grund versetzten lebenden Gewebe. Albrecht von Graefes Arch Ophthalmol 1873;19:358-373.
  105. Medawar PB: Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol 1948;29:58-69.
  106. Kaplan HJ, Streilein JW , Stevens TR: Transplantation immunology of the anterior chamber of the eye. II. Immune response to allogeneic cells. J Immunol 1975;115:805-810.
  107. Niederkorn JY: Immune privilege in the anterior chamber of the eye. Crit Rev Immunol 2002;22:13-46.
  108. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:879-889.
  109. D'Orazio TJ, Niederkorn JY: A novel role for TGF-beta and IL-10 in the induction of immune privilege. J Immunol 1998;160:2089-2098.
  110. Kosiewicz MM, Alard P , Streilein JW: Alterations in cytokine production following intraocular injection of soluble protein antigen: impairment in IFN-gamma and induction of TGF-beta and IL-4 production. J Immunol 1998;161:5382-5390.
  111. Li XY , D'Orazio LT, Niederkorn JY: Role of Th1 and Th2 cells in anterior chamber-associated immune deviation. Immunology 1996;89:34-40.
  112. Katagiri K, Zhang-Hoover J, Mo JS, Stein-Streilein J, Streilein JW: Using tolerance induced via the anterior chamber of the eye to inhibit Th2-dependent pulmonary pathology. J Immunol 2002;169:84-89.
  113. Whittum JA, Niederkorn JY, McCulley JP, Streilein JW: Intracameral inoculation of herpes sim- plex virus type I induces anterior chamber associated immune deviation. Curr Eye Res 1982;2:691-697.
  114. Egan RM, Yorkey C, Black R, et al: Peptide-specific T cell clonal expansion in vivo following immunization in the eye, an immune-privileged site. J Immunol 1996;157:2262-2271.
  115. Sherman SH, Green K, Laties AM: The fate of anterior chamber fluorescein in the monkey eye. 1. The anterior chamber outflow pathways. Exp Eye Res 1978;27:159-173.
  116. Faunce DE, Sonoda KH, Stein-Streilein J: MIP-2 recruits NKT cells to the spleen during tolerance induction. J Immunol 2001;166:313-321.
  117. Griffith TS, Yu X, Herndon JM, Green DR, Ferguson TA: CD95-induced apoptosis of lympho- cytes in an immune privileged site induces immunological tolerance. Immunity 1996;5:7-16.
  118. Kawashima H, Yamagami S, Tsuru T, Gregerson DS: Anterior chamber inoculation of splenocytes without Fas/Fas-ligand interaction primes for a delayed-type hypersensitivity response rather than inducing anterior chamber-associated immune deviation. Eur J Immunol 1997;27:2490-2494.
  119. Elzey BD, Griffith TS, Herndon JM, et al: Regulation of Fas ligand-induced apoptosis by TNF. J Immunol 2001;167:3049-3056.
  120. Niederkorn JY, Mayhew E, Mellon J, Hegde S: Role of tumor necrosis factor receptor expression in anterior chamber-associated immune deviation (ACAID) and corneal allograft survival. Invest Ophthalmol Vis Sci 2004;45:2674-2681.
  121. Sohn JH, Bora PS, Suk HJ, et al: Tolerance is dependent on complement C3 fragment iC3b bind- ing to antigen-presenting cells. Nat Med 2003;9:206-212.
  122. Wang Y, Goldschneider I, O'Rourke J, Cone RE: Blood mononuclear cells induce regulatory NK T thymocytes in anterior chamber-associated immune deviation. J Leukoc Biol 2001;69:741-746.
  123. Wilbanks GA, Streilein JW: Studies on the induction of anterior chamber-associated immune deviation (ACAID). 1. Evidence that an antigen-specific, ACAID-inducing, cell-associated signal exists in the peripheral blood. J Immunol 1991;146:2610-2617.
  124. Lin HH, Faunce DE, Stacey M, et al: The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. J Exp Med 2005;201: 1615-1625.
  125. Sonoda KH, Stein-Streilein J: CD1d on antigen-transporting APC and splenic marginal zone B cells promotes NKT cell-dependent tolerance. Eur J Immunol 2002;32:848-857.
  126. Wang Y, Goldschneider I, Foss D, et al: Direct thymic involvement in anterior chamber-associated immune deviation: evidence for a nondeletional mechanism of centrally induced tolerance to extrathymic antigens in adult mice. J Immunol 1997;158:2150-2155.
  127. Goldschneider I, Cone RE: A central role for peripheral dendritic cells in the induction of acquired thymic tolerance. Trends Immunol 2003;24:77-81.
  128. Sonoda KH, Exley M, Snapper S, Balk SP, Stein-Streilein J: CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site. J Exp Med 1999;190:1215-1226.
  129. Sonoda KH, Faunce DE, Taniguchi M, et al: NK T cell-derived IL-10 is essential for the differen- tiation of antigen-specific T regulatory cells in systemic tolerance. J Immunol 2001;166:42-50.
  130. Niederkorn J: Immune privilege of the eye; in Chan LS (ed): Animal Models of Human Inflammatory Skin Diseases. New York, CRC Press, 2004, p 564.
  131. Streilein JW, Niederkorn JY: Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J Exp Med 1981;153:1058-1067.
  132. Faunce DE, Stein-Streilein J: NKT cell-derived RANTES recruits APCs and CD8ϩ T cells to the spleen during the generation of regulatory T cells in tolerance. J Immunol 2002;169:31-38.
  133. Nakamura T, Terajewicz A, Stein-Streilein J: Mechanisms of peripheral tolerance following intra- cameral inoculation are independent of IL-13 or STAT6. J Immunol 2005;175:2643-2646.
  134. D'Orazio TJ, Niederkorn JY: Splenic B cells are required for tolerogenic antigen presentation in the induction of anterior chamber-associated immune deviation (ACAID). Immunology 1998;95:47-55.
  135. Niederkorn JY, Mayhew E: Role of splenic B cells in the immune privilege of the anterior cham- ber of the eye. Eur J Immunol 1995;25:2783-2787.
  136. Skelsey ME, Mayhew E, Niederkorn JY: Splenic B cells act as antigen presenting cells for the induction of anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci 2003;44: 5242-5251.
  137. D'Orazio TJ, Mayhew E, Niederkorn JY: Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1. J Immunol 2001;166:26-32.
  138. Hara Y, Okamoto S, Rouse B, Streilein JW: Evidence that peritoneal exudate cells cultured with eye-derived fluids are the proximate antigen-presenting cells in immune deviation of the ocular type. J Immunol 1993;151:5162-5171.
  139. Noble A, Zhao ZS, Cantor H: Suppression of immune responses by CD8 cells. II. Qa-1 on acti- vated B cells stimulates CD8 cell suppression of T helper 2 responses. J Immunol 1998;160: 566-571.
  140. Cai JL, Tucker PW: Gamma-delta T cells: immunoregulatory functions and immunoprotection; in Bergstresser PR, Takashima A (eds): Gamma-Delta T Cells. Chem Immunol. Basel, Karger, 2001, vol 79, pp 99-138.
  141. Holtmeier W, Kabelitz D: ␥␦ T cells link innate and adaptive immune responses; in Kabelitz D, Schröder JM (eds): Mechanisms of Epithelial Defense. Chem Immunol Allergy. Basel, Karger, 2005, vol 86, pp 151-183.
  142. Skelsey ME, Mellon J, Niederkorn JY: ␥␦ T cells are needed for ocular immune privilege and corneal graft survival. J Immunol 2001;166:4327-4333.
  143. Xu Y, Kapp JA: ␥␦ T cells are critical for the induction of anterior chamber-associated immune deviation. Immunology 2001;104:142-148.
  144. Brandes M, Willimann K, Moser B: Professional antigen-presentation function by human ␥␦ T cells. Science 2005;309:264-268.
  145. Bellinger DL, Lorton D, Romano TD, et al: Neuropeptide innervation of lymphoid organs. Ann NY Acad Sci 1990;594:17-33.
  146. Madden KS, Felten SY, Felten DL, Sundaresan PR, Livnat S: Sympathetic neural modulation of the immune system. I. Depression of T cell immunity in vivo and vitro following chemical sym- pathectomy. Brain Behav Immun 1989;3:72-89.
  147. Rice PA, Boehm GW, Moynihan JA, Bellinger DL, Stevens SY: Chemical sympathectomy increases the innate immune response and decreases the specific immune response in the spleen to infection with Listeria monocytogenes. J Neuroimmunol 2001;114:19-27.
  148. Rook GA, Lightman SL, Heijnen CJ: Can nerve damage disrupt neuroendocrine immune home- ostasis? Leprosy as a case in point. Trends Immunol 2002;23:18-22.
  149. Li X, Taylor S, Zegarelli B, et al: The induction of splenic suppressor T cells through an immune- privileged site requires an intact sympathetic nervous system. J Neuroimmunol 2004;153:40-49.
  150. Vella AT, Scherer MT, Schultz L, Kappler JW, Marrack P: B cells are not essential for peripheral T-cell tolerance. Proc Natl Acad Sci USA 1996;93:951-955.
  151. Wilbanks GA, Streilein JW: Characterization of suppressor cells in anterior chamber-associated immune deviation (ACAID) induced by soluble antigen. Evidence of two functionally and pheno- typically distinct T-suppressor cell populations. Immunology 1990;71:383-389. References
  152. Bron AJ, Tripathi DM, Tripati BJ: Wolff's anatomy of the eye and orbit. London, Chapman & Hall Medical, 1997.
  153. Argueso P , Gipson IK: Epithelial mucins of the ocular surface: structure, biosynthesis and func- tion. Exp Eye Res 2001;73:281-289.
  154. Cursiefen C, Schlotzer-Schrehardt U, Kuchle M, Sorokin L, Breiteneder-Geleff S, Alitalo K, Jackson D: Lymphatic vessels in vascularized human corneas: immunohistochemical investiga- tion using LYVE-1 and podoplanin. Invest Ophthalmol Vis Sci 2002;43:2127-2135.
  155. Hamrah P, Zhang Q, Liu Y, Dana MR: Novel characterization of MHC class II-negative population of resident corneal Langerhans cell-type dendritic cells. Invest Ophthalmol Vis Sci 2002;43: 639-646.
  156. Kraal G, Mebius RE: High endothelial venules: lymphocyte traffic control and controlled traffic. Adv Immunol 1997;65:347-395.
  157. Knop N, Knop E: Conjunctiva-associated lymphoid tissue in the human eye. Invest Ophthalmol Vis Sci 2000;41:1270-1279.
  158. Knop E, Knop N: The role of eye-associated lymphoid tissue in corneal immune protection. J Anat 2005;206:271-285.
  159. Allansmith MR, Greiner JV , Baird RS: Number of inflammatory cells in the normal conjunctiva. Am J Ophthalmol 1978;86:250-259.
  160. 9 Sacks EH, Wieczorek R, Jakobiec FA, Knowles DM: Lymphocytic subpopulations in the normal human conjunctiva. A monoclonal antibody study. Ophthalmology 1986;93:1276-1283.
  161. Dua HS, Gomes JA, Jindal VK, Appa SN, Schwarting R, Eagle RC Jr, Donoso LA, Laibson PR: Mucosa specific lymphocytes in the human conjunctiva, corneoscleral limbus and lacrimal gland. Curr Eye Res 1994;13:87-93.
  162. Hingorani M, Metz D, Lightman SL: Characterisation of the normal conjunctival leukocyte popu- lation. Exp Eye Res 1997;64:905-912.
  163. Kessing SV: Mucous gland system of the conjunctiva. A quantitative normal anatomical study. Acta Ophthalmol (Copenh) 1968;95(suppl):1-133.
  164. Osterlind G: An investigation into the presence of lymphatic tissue in the human conjunctiva, and its biological and clinical importance. Acta Ophthalmol (Copenh) 1944;23(suppl):1-79.
  165. Knop E, Claus P, Knop N: Eye-associated lymphoid tissue (EALT): RT-PCR verifies the presence of mRNA for IgA and its transporter (secretory component) in the normal human conjunctiva. Invest Ophthalmol Vis Sci 2003;44:S3801.
  166. Brandtzaeg P, Farstad IN: The human mucosal B-cell system; in Ogra PL, Mestecky J, Lamm ME, Strober W, McGhee JR, Bienenstock J (eds): Handbook of Mucosal Immunology, ed 2. San Diego, Academic Press, 1999, pp 439-468.
  167. Gillette TE, Chandler JW, Greiner JV: Langerhans cells of the ocular surface. Ophthalmology 1982;89:700-711.
  168. Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998;392:245-252.
  169. Morgan SJ, Williams JH, Walls AF, Church MK, Holgate ST, McGill JI: Mast cell numbers and staining characteristics in the normal and allergic human conjunctiva. J Allergy Clin Immunol 1991;87:111-116.
  170. Stahl JL, Cook EB, Barney NP, Graziano FM: Pathophysiology of ocular allergy: the roles of con- junctival mast cells and epithelial cells. Curr Allergy Asthma Rep 2002;2:332-339.
  171. Chodosh J, Nordquist RE, Kennedy RC: Comparative anatomy of mammalian conjunctival lym- phoid tissue: a putative mucosal immune site. Dev Comp Immunol 1998;22:621-630.
  172. Knop N, Knop E: Ultrastructural anatomy of CALT follicles in the rabbit reveals characteristics of M-cells, germinal centres and high endothelial venules. J Anat 2005;207:409-426.
  173. Wieczorek R, Jakobiec FA, Sacks EH, Knowles DM: The immunoarchitecture of the normal human lacrimal gland. Relevancy for understanding pathologic conditions. Ophthalmology 1988;95: 100-109.
  174. Franklin RM, Kenyon KR, Tomasi TB Jr: Immunohistologic studies of human lacrimal gland: localization of immunoglobulins, secretory component and lactoferrin. J Immunol 1973;110: 984-992.
  175. Sullivan DA: Ocular mucosal immunity; in Ogra PL, Mestecky J, Lamm ME, Strober W, McGhee J, Bienenstock J (eds): Handbook of Mucosal Immunology, ed 2. San Diego, Academic Press, 1999, pp 1241-1281.
  176. Knop E, Knop N: Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system. Invest Ophthalmol Vis Sci 2001;42:566-574.
  177. Knop E, Knop N: MALT tissue of the conjunctiva and nasolacrimal system in the rabbit and human. Vis Res 1996;36:S60.
  178. Paulsen FP, Paulsen JI, Thale AB, Schaudig U, Tillmann BN: Organized mucosa-associated lym- phoid tissue in human naso-lacrimal ducts. Adv Exp Med Biol 2002;506:873-876.
  179. Knop E, Knop N: Human lacrimal drainage-associated lymphoid tissue (LDALT) belongs to the common mucosal immune system. Adv Exp Med Biol 2002;506:861-866.
  180. Sack RA, Conradi L, Krumholz D, Beaton A, Sathe S, Morris C: Membrane array characterization of 80 chemokines, cytokines, and growth factors in open-and closed-eye tears: angiogenin and other defense system constituents. Invest Ophthalmol Vis Sci 2005;46:1228-1238.
  181. Knop E, Knop N: A functional unit for ocular surface immune defense formed by the lacrimal gland, conjunctiva and lacrimal drainage system. Adv Exp Med Biol 2002;506:835-844.
  182. Medzhitov R, Janeway CA Jr: Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 1997;9:4-9.
  183. Johnson AC, Heinzel FP, Diaconu E, Sun Y, Hise AG, Golenbock D, Lass JH, Pearlman E: Activation of Toll-like receptor (TLR)2, TLR4, and TLR9 in the mammalian cornea induces MyD88-dependent corneal inflammation. Invest Ophthalmol Vis Sci 2005;46:589-595.
  184. Zhang J, Xu K, Ambati B, Yu FS: Toll-like receptor 5-mediated corneal epithelial inflammatory responses to Pseudomonas aeruginosa flagellin. Invest Ophthalmol Vis Sci 2003;44:4247-4254.
  185. Ueta M, Nochi T, Jang MH, Park EJ, Igarashi O, Hino A, Kawasaki S, Shikina T, Hiroi T, Kinoshita S, Kiyono H: Intracellularly expressed TLR2s and TLR4s contribution to an immunosilent environ- ment at the ocular mucosal epithelium. J Immunol 2004;173:3337-3347.
  186. McIntosh RS, Cade JE, Al Abed M, Shanmuganathan V, Gupta R, Bhan A, Tighe PJ, Dua HS: The spectrum of antimicrobial peptide expression at the ocular surface. Invest Ophthalmol Vis Sci 2005;46:1379-1385.
  187. Ni M, Evans DJ, Hawgood S, Anders EM, Sack RA, Fleiszig SM: Surfactant protein D is present in human tear fluid and the cornea and inhibits epithelial cell invasion by Pseudomonas aerugi- nosa. Infect Immun 2005;73:2147-2156.
  188. Langer G, Jagla W, Behrens-Baumann W, Walter S, Hoffmann W: Secretory peptides TFF1 and TFF3 synthesized in human conjunctival goblet cells. Invest Ophthalmol Vis Sci 1999;40:2220-2224.
  189. Paulsen FP, Pufe T, Schaudig U, Held-Feindt J, Lehmann J, Schroder JM, Tillmann BN: Detection of natural peptide antibiotics in human nasolacrimal ducts. Invest Ophthalmol Vis Sci 2001;42: 2157-2163.
  190. Camelo S, Shanley A, Voon ASP, McMenamin PG: The distribution of antigen in lymphoid tissues following ist injection into the anterior chamber of the rat eye. J Immunol 2004;172:5388-5395.
  191. Yamagami S, Dana MR: The critical role of lymph nodes in corneal alloimmunization and graft rejection. Invest Ophthalmol Vis Sci 2001;42:1293-1298.
  192. Hazlett LD, McClellan SM, Hume EB, Dajcs JJ, O'Callaghan RJ, Willcox MD: Extended wear contact lens usage induces Langerhans cell migration into cornea. Exp Eye Res 1999;69:575-577.
  193. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:879-889.
  194. Calder VL, Lackie PM: Basic science and pathophysiology of ocular allergy. Curr Allergy Asthma Rep 2004;4:326-331.
  195. Dana MR, Qian Y, Hamrah P: Twenty-five-year panorama of corneal immunology: emerging con- cepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection. Cornea 2000;19:625-643.
  196. Annacker O, Pimenta-Araujo R, Burlen-Defranoux O, Bandeira A: On the ontogeny and physiol- ogy of regulatory T cells. Immunol Rev 2001;182:5-17.
  197. Bienenstock J, McDermott M, Befus D, O'Neill M: A common mucosal immunologic system involving the bronchus, breast and bowel. Adv Exp Med Biol 1978;107:53-59.
  198. Mestecky J, McGhee JR, Michalek SM, Arnold RR, Crago SS, Babb JL. Concept of the local and common mucosal immune response. Adv Exp Med Biol 1978;107:185-192.
  199. Niederkorn JY, Streilein JW: Induction of anterior chamber-associated immune deviation (ACAID) by allogeneic intraocular tumors does not require splenic metastases. J Immunol 1982;128: 2470-2474.
  200. McGhee JR, Lamm ME, Strober W: Mucosal immune responses. An overview; in Ogra PL, Mestecky J, Lamm ME, Strober W, McGhee JR, Bienenstock J (eds): Handbook of Mucosal Immunology, ed 2. San Diego, Academic Press, 1999, pp 485-506.
  201. Knop E, Knop N, Pleyer U: Clinical aspects of MALT; in Pleyer U, Mondino B (eds): Uveitis and Immunological Disorders, ed 1. Berlin, Springer, 2004, pp 67-89.
  202. Knop E, Knop N: Influence of the eye-associated lymphoid tissue (EALT) on inflammatory ocu- lar surface disease. Ocul Surface 2005;3:S180-S186.
  203. Sack RA, Beaton A, Sathe S, Morris C, Willcox M, Bogart B: Towards a closed eye model of the pre-ocular tear layer. Prog Retin Eye Res 2000;19:649-668. References
  204. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:879-889.
  205. Streilein JW: Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 2003;74:179-185.
  206. Cursiefen C, Kruse FE: New aspects of corneal angiogenesis; in Reinhard T, Larkin F (eds): Cornea and External Eye; in Krieglstein GK, Weinreb RN (ser eds): Essentials in Ophthalmology. New York, Springer, 2006, pp 83-99.
  207. Chang JH, Gabison EE, Kato T, Azar DT: Corneal neovascularization. Curr Opin Ophthalmol 2001;12:242-249.
  208. Streilein JW , Y amada J, Dana MR, Ksander BR: Anterior chamber-associated immune deviation, ocular immune privilege, and orthotopic corneal allografts. Transplant Proc 1999;31:1472-1475.
  209. Niederkorn JY: The immune privilege of corneal allografts. Transplantation 1999;67:503-508.
  210. Streilein JW: New thoughts on the immunology of corneal transplantation. Eye 2003;17:943-948.
  211. Cursiefen C, Chen L, Dana MR, Streilein JW: Corneal lymphangiogenesis: evidence, mechanisms and implications for transplant immunology. Cornea 2003;22:273-281.
  212. Cursiefen C, Maruyama K, Liu Y, Chen L, Jackson D, Wiegand S, Dana MR, Streilein JW: Inhibition of hemangiogenesis and lymphangiogenesis after normal-risk corneal transplanta- tion by neutralizing VEGF promotes graft survival. Invest Ophthalmol Vis Sci 2004;45: 2666-2673.
  213. Cursiefen C, Chen L, Borges L, Jackson D, Cao J, Radziejewski C, D'Amore PA, Dana MR, Wiegand SJ, Streilein JW: VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest 2004;113:1040-1050.
  214. Hori J, Jouyce N, Streilein JW: Epithelium-deficient corneal allografts display immune privilege beneath the kidney capsule. Invest Ophthalmol Vis Sci 2000;41:443-452.
  215. Cursiefen C, Masli S, Ng TF, Dana MR, Bornstein P, Lawler J, Streilein JW: Roles of throm- bospondin 1 and 2 in regulating spontaneous and induced angiogenesis in the cornea and iris. Invest Ophthalmol Vis Sci 2004;45:1117-1124.
  216. Dana MR, Streilein JW: Loss and restoration of immune privilege in eyes with corneal neovascu- larization. Invest Ophthalmol Vis Sci 1996;37:2485-2494.
  217. Chen L, Hamrah P, Cursiefen C, Jackson D, Streilein JW, Dana MR: Vascular endothelial growth factor receptor-3 (VEGFR-3) mediates dendritic cell migration to lymph nodes and induction of immunity to corneal transplants. Nat Med 2004;10:813-815.
  218. Cao J, Renard R, Song H, Ioffe E, Mosher V, Rudge JS, Koehler-Stec EM, Yancopoulos GD, Wiegand SJ: Inhibition of IL-1 blocks corneal inflammation and neovascularization. Invest Ophthalmol Vis Sci 2003;44:E823.
  219. Maruyama K, Li M, Cursiefen C, Jackson DG, Keino H, Tomita M, Van Rooijen N, Takenaka H, D'Amore PA, Stein-Streilein J, Losordo DW, Streilein JW: Inflammation-induced lymphan- giogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest 2005;115: 2363-2372.
  220. Diaz-Araya CM, Madigan MC, Provis JM, Penfold PL: Immunohistochemical and topographic studies of dendritic cells and macrophages in human fetal cornea. Invest Ophthalmol Vis Sci 1995;36:644-656.
  221. Hamrah P, Zhang Q, Liu Y, Dana MR: Novel characterization of MHC class II-negative population of resident corneal Langerhans cell-type dendritic cells. Invest Ophthalmol Vis Sci 2002;43: 639-646.
  222. Brisette-Storkus C, Reynolds S, Lepisto A, Hendricks RL: Identification of a novel macrophage population in the normal mouse corneal stroma. Invest Ophthalmol Vis Sci 2002;43:2264-2271.
  223. Lai CM, Brankov M, Zaknich T, Lai YK, Shen WY, Constable IJ, Kovesdi I, Rakoczy PE: Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization. Hum Gene Ther 2001;12:1299-1310.
  224. Fannon M, Forsten-Willimas K, Dowd CJ, Freedmann DA, Folkman J, Nugent MA: Binding inhi- bition of angiogenic factors by heparan sulfate proteoglycans in aqueous humor: potential mecha- nism for maintenance of an avascular environment. FASEB J 2003;17:902-904.
  225. Sano Y, Ksander BR, Streilein JW: Fate of orthotopic corneal allografts in eyes that cannot support anterior chamber-associated immune deviation induction. Invest Ophthalmol Vis Sci 1995;36: 2176-2185.
  226. Maguire MG, Stark WJ, Gottsch JD, Stulting RD, Sugar A, Fink NE, Schwartz A; Collaborative Corneal Transplantation Studies Research Group: Risk factors for corneal graft failure and rejec- tion in the collaborative corneal transplantation studies. Ophthalmology 1994;101:1536-1547.
  227. Cursiefen C, Wenkel H, Martus P, Langenbucher A, Nguyen N, Seitz B, Küchle M, Naumann GOH: Impact of short-term versus long-term topical steroids on corneal neovascularization after non-high-risk keratoplasty. Graefes Arch Clin Exp Ophthalmol 2001;239:514-521.
  228. Bachmann B, Lütjen-Drecoll E, Wiegand SJ, Streilein JW, Kruse FE, Cursiefen C: Inhibition of angiogenesis and lymphangiogenesis after high-risk keratoplasty by neutralizing VEGF-A improves corneal graft survival. Invest Ophthalmol Vis Sci 2005;46:E4743.
  229. Slegers TP, van der Gaag R, van Rooijen N, van Rij G, Streilein JW: Effect of local macrophage depletion on cellular immunity and tolerance evoked by corneal allografts. Curr Eye Res 2003;26:73-79.
  230. Cursiefen C, Schlötzer-Schrehardt U, Küchle M, Sorokin L, Breitender-Geleff S, Alitalo K, Jackson D: Lymphatic vessels in vascularized human corneas: immunohistochemical investiga- tion using LYVE-1 and podoplanin. Invest Ophthalmol Vis Sci 2002;43:2127-2135.
  231. Cursiefen C, Ikeda S, Nishina PM, Smith RS, Ikeda A, Jackson D, Mo JS, Chen L, Dana RM, Pytowski B, Kruse FE, Streilein JW: Spontaneous corneal hem-and lymphangiogenesis in mice with destrin-mutation depend on VEGFR3 signaling. Am J Pathol 2005;166:1367-1377.
  232. Zheng M, Schwarz MA, Lee S, Kumaraguru U, Rouse BT: Control of stromal keratitis by inhibi- tion of neovascularization. Am J Pathol 2001;159:1021-1029.
  233. Cursiefen C, Chen L, Saint-Geniez M, Hamrah P, Jin Y, Rashid S, Pytowski B, Persaud K, Wu Y, Streilein JW, Dana R: Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision. Proc Natl Acad Sci 2006;103:11405-11410.
  234. Dr. Claus Cursiefen, FEBO Department of Ophthalmology, Friedrich Alexander University Erlangen-Nürnberg Schwabachanlage 6 DE-91054 Erlangen (Germany)
  235. Tel. ϩ49 9131 8533001, Fax ϩ49 9131 8536401, E-Mail ccursiefen@yahoo.com References
  236. Langerhans P: Über die Nerven der menschlichen Haut. Virchows Arch Pathol Anat Physiol 1868;44:325-337.
  237. Silberberg I: Apposition of mononuclear cells to Langerhans cells in contact allergic reactions. An ultrastructural study. Acta Derm Venereol 1973;53:1-12.
  238. Engelmann TW: Über die Hornhaut des Auges. Leipzig, Universita ¯t Leipzig, 1867. Ranvier L: Cornée; in Ranvier L (ed): Leçons d'anatomie générale faites au Collège de France. Paris, Baillière, 1881, pp 1878-1879.
  239. Egorow I: Nervenelemente der Cornea im Meerschweinchenauge. Graefes Arch Ophthalmol 1934;131:531-553.
  240. Liu, YJ: Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell 2001;106:259-262.
  241. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767-811.
  242. Gillette TE, Chandler JW , Greiner JV: Langerhans cells of the ocular surface. Ophthalmology 1982;89:700-711.
  243. Jager MJ: Corneal Langerhans cells and ocular immunology. Reg Immunol 1992;4:186-195.
  244. Peeler JS, Niederkorn JY: Antigen presentation by Langerhans cells in vivo: donor-derived Ia ϩ Langerhans cells are required for induction of delayed-type hypersensitivity but not for cytotoxic T lymphocyte responses to alloantigens. J Immunol 1986;136:4362-4371.
  245. Rowden G: Expression of Ia antigens on Langerhans cells in mice, guinea pigs, and man. J Invest Dermatol 1980;75:22-31.
  246. Streilein JW, Toews GB, Bergstresser PR: Corneal allografts fail to express Ia antigens. Nature 1979;282:320-321.
  247. Streilein JW: Regional immunity and ocular immune privilege; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol Basel, Karger, 1999, vol 73, pp 11-38.
  248. Pepose JS, Gardner KM, Nestor MS, Foos RY, Pettit TH: Detection of HLA class I and II antigens in rejected human corneal allografts. Ophthalmology 1985;92:1480-1484.
  249. Rocha G, Deschênes J, Rowsey JJ: The immunology of corneal graft rejection. Crit Rev Immunol 1998;18:305-325.
  250. Haftek M, Faure M, Schmitt D, Thivolet J: Langerhans cells in skin from patients with psoriasis: quantitative and qualitative study of T6 and HLA-DR antigen-expressing cells and changes with aromatic retinoid administration. J Invest Dermatol 1983;81:10-14.
  251. Hamrah P, Liu Y, Zhang Q, Dana MR: Alterations in corneal stromal dendritic cell phenotype and distribution in inflammation. Arch Ophthalmol 2003;121:1132-1140.
  252. Hamrah P, Zhang Q, Liu Y, Dana MR: Novel characterization of MHC class II-negative population of resident corneal Langerhans cell-type dendritic cells. Invest Ophthalmol Vis Sci 2002;43: 639-646.
  253. Brissette-Storkus CS, Reynolds SM, Lepisto AJ, Hendricks RL: Identification of a novel macrophage population in the normal mouse corneal stroma. Invest Ophthalmol Vis Sci 2002;43: 2264-2271.
  254. Liu Y, Hamrah P, Zhang Q, Taylor AW, Dana MR: Draining lymph nodes of corneal transplant hosts exhibit evidence for donor major histocompatibility complex (MHC) class II-positive den- dritic cells derived from MHC class II-negative grafts. J Exp Med 2002;195:259-268.
  255. Steinman RM, Cohn ZA: Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973;137:1142-1162.
  256. Steinman RM: The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 1991;9:271-296.
  257. Hart DNJ: Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 1997;90:3245-3287.
  258. Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998;392:245-252.
  259. Lanzavecchia A, Sallusto F: The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics. Curr Opin Immunol 2001;13:291-298.
  260. Thomson AW, Lu L, Murase N, Demetris AJ, Rao AS, Starzl TE: Microchimerism, dendritic cell progenitors and transplantation tolerance. Stem Cells 1995;13:622-639.
  261. Thomson AW, Lu L: Dendritic cells as regulators of immune reactivity: implications for trans- plantation. Transplantation 1999;68:1-8.
  262. Steinman RM, Nussenzweig MC: Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci USA 2002;99:351-358.
  263. Rescigno M, Borrow P: The host-pathogen interaction: new themes from dendritic cell biology. Cell 2001;106:267-270.
  264. Palucka K, Banchereau J: How dendritic cells and microbes interact to elicit or subvert protective immune responses. Curr Opin Immunol 2002;14:420-431.
  265. Liu YJ, Kanzler H, Soumelis V, Gilliet M: Dendritic cell lineage, plasticity and cross-regulation. Nat Immunol 2001;2:585-589.
  266. Cella M, Sallusto F, Lanzavecchia A: Origin, maturation and antigen presentation function of den- dritic cells. Curr Opin Immunol 1997;9:10-16.
  267. Austyn JM: New insights into the mobilization and phagocytic activity of dendritic cells. J Exp Med 1996;183:1287-1292.
  268. Austyn JM, Hankins DF, Larsen CP, Morris PJ, Rao AS, Roake JA: Isolation and characterization of dendritic cells from mouse heart and kidney. J Immunol 1994;152:2401-2410.
  269. Larsen CP, Ritchie SC, Hendrix R, Lindsey PS, Hathcock KS, Hodes RJ, Lowry RP, Pearson TC: Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expres- sion on murine dendritic cells. J Immunol 1994;152:5208-5219.
  270. Mellman I, Steinman RM: Dendritic cells: specialized and regulated antigen processing machines. Cell 2001;106:255-258.
  271. Dana MR, Streilein JW: Loss and restoration of immune privilege in eyes with corneal neovascu- larization. Invest Ophthalmol Vis Sci 1996;37:2485-2494.
  272. Jager MJ, Atherton SS, Bradley D, Streilein JW: Herpetic stromal keratitis in mice: less reversibil- ity in the presence of Langerhans cells in the central cornea. Curr Eye Res 1991;10:69-73.
  273. McLeish W, Rubsamen P, Atherton SS, et al: Immunobiology of Langerhans cells on the ocular surface. II. Role of central corneal Langerhans cells in stromal keratitis following experimental HSV-1 infection in mice. Reg Immunol 1989;2:236-243.
  274. Hazlett LD: Pathogenic mechanisms of P. aeruginosa keratitis: a review of the role of T cells, Langerhans cells, PMN, and cytokines. DNA Cell Biol 2002;21:383-390. Niederkorn JY: The immune privilege of corneal allografts. Transplantation 1999;67: 1503-1508.
  275. Niederkorn JY, Peeler JS, Ross J, Callanan D: The immunogenic privilege of corneal allografts. Reg Immunol 1989;2:117-124.
  276. Streilein JW: Immunobiology and immunopathology of corneal transplantation; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 186-206.
  277. Klareskog L, Forsum U, Malmnäs T, Rask L, Peterson PA: Expression of Ia antigen-like molecules on cells in the corneal epithelium. Invest Ophthalmol Vis Sci 1979;18:310-313.
  278. Zhivov A, Stave J, Vollmar B, Guthoff R: In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the normal human corneal epithelium. Graefes Arch Clin Exp Ophthalmol 2005;243:1056-1061.
  279. Hamrah P, Liu Y, Zhang Q, Dana MR: The corneal stroma is endowed with significant numbers of resident dendritic cells. Invest Ophthalmol Vis Sci 2003;44:581-589.
  280. Nakamura T, Ishikawa F, Sonoda KH, Hisatomi T, Qiao H, Yamada J, Fukata M, Ishibashi T, Harada M, Kinoshita S: Characterization and distribution of bone marrow-derived cells in the mouse cornea. Invest Ophthalmol Vis Sci 2005;46:497-503.
  281. Dana MR: Corneal antigen-presenting cells: diversity, plasticity and disguise: the Cogan lecture. Invest Ophthalmol Vis Sci 2004;45:722-727.
  282. Novak N, Siepmann K, Zierhut M, Bieber T: The good, the bad and the ugly -APCs of the eye. Trends Immunol 2003;24:570-574.
  283. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2004;3:879-889.
  284. Inaba K, Steinman RM, Witmer Pack M, Aya H, Inaba M, Sudo T, Wolpe S, Schuler G: Identification of proliferating dendritic cell precursors in mouse blood. J Exp Med 1992;175: 1157-1167.
  285. O'Keeffe M, Hochrein H, Vremec D, Scott B, Hertzog P, Tatarczuch L, Shortman K: Dendritic cell precursor populations of mouse blood: identification of the murine homologues of human blood plasmacytoid pre-DC2 and CD11c ϩ DC1 precursors. Blood 2003;101:1453-1459, erratum 2003;101:3364.
  286. Hamrah P, Huq SO, Liu Y, Zhang Q, Dana MR: Corneal immunity is mediated by heterogeneous population of antigen-presenting cells. J Leukoc Biol 2003;74:172-178.
  287. Santambrogio L, Belyanskaya SL, Fischer FR, Cipriani B, Brosnan CF, Ricciardi-Castagnoli P, Stern LJ, Strominger JL, Riese R: Developmental plasticity of CNS microglia. Proc Natl Acad Sci USA 2001;98:6295-6300.
  288. McKnight AJ, Gordon S: Membrane molecules as differentiation antigens of murine macrophages. Adv Immunol 1998;68:271-314.
  289. Morrissette N, Gold E, Aderm A: The macrophage: a cell for all seasons. Trends Cell Biol 1999;9: 199-201.
  290. van Rooijen N, Wijburg OL, van den Dobbelsteen GP, Sanders A: Macrophages in host defense mechanisms. Curr Top Microbiol Immunol 1996;210:159-165.
  291. Unanue ER: Antigen-presenting function of the macrophage. Annu Rev Immunol 1984;2:395-428.
  292. Adams DO: Macrophage activation; in Roitt IM, Delves PJ (eds): Encyclopedia of Immunology. London, Academic Press, 1992, pp 1020-1026.
  293. Hingorani M, Metz D, Lightman SL: Characterization of the normal conjunctival leukocyte popu- lation. Exp Eye Res 1997;64:905-912.
  294. Sacks E, Rutgers J, Jakobiec FA, Bonetti F, Knowles DM: A comparison of conjunctival and nonoc- ular dendritic cells utilizing new monoclonal antibodies. Ophthalmology 1986;93: 1089-1097.
  295. Caux C, Dezutter-Dambuyant C, Schmidt D, Banchereau J: GM-CSF and TNF-␣ cooperate in the generation of dendritic Langerhans cells. Nature 1992;360:258-261.
  296. Cumberbatch M, Dearman RJ, Kimber I: Langerhans cells require signals from both tumor necro- sis factor-␣ and interleukin-1␤ for migration. Immunology 1997;92:388-395.
  297. Reis e Sousa C: Dendritic cells as sensors of infection. Immunity 2001;14:495-498.
  298. Srivastava P: Interaction of heat shock proteins with peptides and antigen presenting cells: chaper- oning of the innate and adaptive immune responses. Annu Rev Immunol 2002;20:395-425.
  299. Dana MR, Yamada J, Streilein JW: Topical interleukin 1 receptor antagonist promotes corneal transplant survival. Transplantation 1997;63:1501-1507.
  300. Dana MR, Dai R, Zhu SN, Yamada J, Streilein JW: Interleukin-1 receptor antagonist suppresses Langerhans cell activity and promotes ocular immune privilege. Invest Ophthalmol Vis Sci 1998;39:70-77.
  301. Dana MR, Zhu SN, Yamada J: Topical modulation of interleukin-1 activity in corneal neovascular- ization. Cornea 1998;17:403-409.
  302. Dekaris I, Yamada J, Streilein JW, Dana MR: Effect of topical interleukin-1 receptor antagonist (IL-1ra) on corneal allograft transplant survival in presensitized hosts. Curr Eye Res 1999;19: 456-459.
  303. Dekaris I, Zhu SN, Dana MR: TNF-␣ regulates corneal Langerhans cell migration. J Immunol 1999;162:4235-4239.
  304. Qian Y, Dekaris I, Yamagami S, Dana MR: Topical soluble tumor necrosis factor receptor type I suppresses ocular chemokine gene expression and rejection of allogeneic corneal transplants. Arch Ophthalmol 2000;118:1666-1671.
  305. Yamada J, Dana MR, Zhu SN, Alard P, Streilein JW: Interleukin 1 receptor antagonist suppresses allosensitization in corneal transplantation. Arch Ophthalmol 1998;116:1351-1357.
  306. Zhu S, Dekaris I, Duncker G, Dana MR: Early expression of proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha after corneal transplantation. J. Interferon Cytokine Res 1999;19:661-669.
  307. Iwata M, Kiritoshi A, Roat MI, Yagihashi A, Thoft RA: Regulation of HLA class II antigen expression on cultured corneal epithelium by interferon-gamma. Invest Ophthalmol Vis Sci 1992;33:2714-2721.
  308. Dreizen NG, Whitsett CF, Stulting RD: Modulation of HLA antigen expression on corneal epithe- lial and stromal cells. InvestOphthalmol Vis Sci 1988;29:933-939.
  309. Young E, Stark WJ, Prendergast RA: Immunology of corneal allograft rejection: HLA-DR anti- gens on human corneal cells. Invest Ophthalmol Vis Sci 1985;26:571-574.
  310. Seo SK, Gebhardt BM, Lim HY, Kang SW, Higaki S, Varnell ED, Hill JM, Kaufman HE, Kwon BS: Murine keratocytes function as antigen-presenting cells. Eur J Immunol 2001;31: 3318-3328.
  311. Gerritsen M: Cytokine activation of human macro-and microvessel-derived endothelial cells. Blood Cells 1993;19:325.
  312. Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, D'Amore PA, Dana MR, Wiegand SJ, Streilein JW: VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflam- matory neovascularization via macrophage recruitment. J Clin Invest 2004;113: 1040-1050.
  313. Maruyama K, Ii M, Cursiefen C, Jackson DG, Keino H, Tomita M, Van Rooijen N, Takenaka H, D'Amore PA, Stein-Streilein, J, Losordo DW, Streilein JW: Inflammation-induced lymphangiogene- sis in the cornea arises from CD11b-positive macrophages. J Clin Invest 2005;115: 2363-2372.
  314. Austyn JM, Larsen CP: Migration patterns of dendritic leukocytes. Implications for transplanta- tion. Transplantation 1990;49:1-7.
  315. Roake JA, Rao AS, Morris PJ, Larsen CP, Hankins DF, Austyn JM: Systemic lipopolysaccharide recruits dendritic cell progenitors to nonlymphoid tissues. Transplantation 1995;59:1319-1324.
  316. Yamagami S, Dana MR, Tsuru T: Draining lymph nodes play an essential role in alloimmunity generated in response to high-risk corneal transplantation. Cornea 2002;21:405-409.
  317. Yamagami S, Dana MR: The critical role of draining lymph nodes in corneal allosensitization. Invest Ophthalmol Vis Sci 2001;42:1293-1298.
  318. Collin HB: Corneal lymphatics in alloxan vascularized rabbit eyes. Invest Ophthalmol Vis Sci 1966;5:1-13.
  319. Collin HB: Lymphatic drainage of 131 I-albumin from the vascularized cornea. Invest Ophthalmol Vis Sci 1970;9:146-155.
  320. Hamrah P, Zhang Q, Dana MR: Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in the conjunctiva -a potential link between lymphangiogenesis and leukocyte traf- ficking on the ocular surface. Adv Exp Med Biol 2002;506:851-858.
  321. Hamrah P, Chen L, Cursiefen C, Zhang Q, Joyce NC, Dana MR: Expression of vascular endothe- lial growth factor receptor-3 (VEGFR-3) on monocytic bone marrow-derived cells in the conjunc- tiva. Exp Eye Res 2004;79:553-561.
  322. Hamrah P, Chen L, Zhang Q, Dana MR: Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on dendritic cells in the cornea. Am J Pathol 2003;163:57-68.
  323. Chen L, Hamrah P, Cursiefen C, Zhang Q, Pytowski B, Streilein JW, Dana MR: Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat Med 2004;10: 813-815.
  324. Jussila L, Alitalo K: Vascular growth factors and lymphangiogenesis. Physiol Rev 2002;82: 673-700.
  325. Veikkola T, Alitalo K: VEGFs, receptors and angiogenesis. Semin Cancer Biol 1999;9:211-220.
  326. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K: A novel vascular endothelial growth factor, VEGF-C, is a ligand for the FLT4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 1996;15:290-298.
  327. Achen MG, Jeltsch M, Kukk E, Mäkinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA: Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci USA 1998;95:548-553.
  328. Kukk E, Lymboussaki A, Taira S, Kaipainen A, Jeltsch M, Joukov V, Alitalo K: VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular develop- ment. Development 1996;122:3829-3837.
  329. Huq S, Liu Y, Benichou G, Dana MR: Relevance of the direct pathway of sensitization in corneal transplantation is dictated by the graft bed microenvironment. J Immunol 2004;173:4464-4469.
  330. Boisgérault F, Liu Y, Anosova N, Ehrlich E, Dana MR, Benichou G: Role of CD4 ϩ and CD8 ϩ T cells in allorecognition. Lessons from corneal transplantation. J Immunol 2001;167:1891-1899. Dr. Pedram Hamrah Cornea Service, Mass. Eye and Ear Infirmary, Harvard Medical School 243 Charles Street, Boston, MA 02114 (USA) Tel. ϩ1 617 573 4300, Fax ϩ1 617 573 4300, E-Mail pedram_hamrah@meei.harvard.edu
  331. Niederkorn JY, Kaplan HJ (eds): Immune Response and the Eye. Chem Immunol Allergy. Basel, Karger, 2007, vol 92, pp 71-85
  332. Cousins SW , McCabe MM, Danielpour D, Streilein JW: Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 1991;32:33-43.
  333. Jampel HD, Roche N, Stark WJ, Roberts AB: Transforming growth factor-␤ in human aqueous humor. Curr Eye Res 1990;9:963-969.
  334. Granstein R, Staszewski R, Knisely TL, et al: Aqueous humor contains transforming growth factor-␤ and a small (Ͻ3500 daltons) inhibitor of thymocyte proliferation. J Immunol 1990;144:3021-3026.
  335. Taylor A: A review of the influence of aqueous humor on immunity. Ocul Immunol Inflamm 2003;11:231-241.
  336. Jorgensen JL, Reay P A, Ehrich EW , Davis MM: Molecular components of T -cell recognition. Annu Rev Immunol 1992;10:835-873.
  337. Friedl P , Storim J: Diversity in immune-cell interactions: states and functions of the immunologi- cal synapse. Trends Cell Biol 2004;14:557-567.
  338. Rosmarin D, Strober BE: The potential of interleukin 12 inhibition in the treatment of psoriasis. J Drugs Dermatol 2005;4:318-325.
  339. Chen H, Hendricks RL: B7 costimulatory requirements of T cells at an inflammatory site. J Immunol 1998;160:5045-5052.
  340. 9 June CH, Bluestone JA, Nadler LM, Thompson CB: The B7 and CD28 receptor family. Immunol Today 1994;15:321-331.
  341. Liu Y, Linsley PS: Costimulation of T-cell growth. Curr Opin Immunol 1992;4:265-270.
  342. Lenschow DJ, Walunas TL, Bluestone JA: CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996;14:233-258.
  343. Dutton RW, Bradley LM, Swain SL: T cell memory. Annu Rev Immunol 1998;16:201-223.
  344. Cher DJ, Mosmann TR: Two types of murine helper T cell clone. II. delayed-type hypersensitivity is mediated by Th1 clones. J Immunol 1987;138:3688-3694.
  345. Yoneda Y, Yoshida R: The role of T cells in allografted tumor rejection: IFN-␥ released from T cells is essential for induction of effector macrophages in the rejection site. J Immunol 1998;160:6012-6017.
  346. Trinchieri G, Perussia B: Immune interferon: a pleiotropic lymphokine with multiple effects. Immunol Today 1985;6:131-136.
  347. Farrar MA, Schreiber RD: The molecular cell biology of interferon-␥ and its receptor. Annu Rev Immunol 1993;11:571-611.
  348. Wangoo A, Cook HT, Taylor GM, Shaw RJ: Enhanced expression of type 1 procollagen and trans- forming growth factor-beta in tuberculin induced delayed type hypersensitivity. J Clin Pathol 1995;48:339-345.
  349. Kimura R, Hu H, Stein-Streilein J: Delayed-type hypersensitivity responses regulate collagen deposition in the lung. Immunology 1992;77:550-555.
  350. Dvorak HF, Mihm MC Jr, Dvorak AM, et al: Morphology of delayed-type hypersensitivity reac- tions in man. I. Quantitative description of the inflammatory response. Lab Invest 1974;31: 111-130. Dvorak AM, Mihm MC Jr, Dvorak HF: Morphology of delayed-type hypersensitivity reactions in man. II. Ultrastructural alterations affecting the microvasculature and the tissue mast cells. Lab Invest 1976;34:179-191.
  351. Buchanan KL, Murphy JW: Kinetics of cellular infiltration and cytokine production during the efferent phase of a delayed-type hypersensitivity reaction. Immunology 1997;90:189-197.
  352. Bennett NT, Schultz GS: Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg 1993;165:728-737.
  353. Streilein JW, Takeuchi M, Taylor AW: Immune privilege, T-cell tolerance, and tissue-restricted autoimmunity. Hum Immunol 1997;52:138-143.
  354. Akira S, Takeda K, Kaisho T: Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001;2:675-680.
  355. Akira S, Hemmi H: Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett 2003;85:85-95.
  356. Akira S: Mammalian Toll-like receptors. Curr Opin Immunol 2003;15:5-11.
  357. Qi H, Denning TL, Soong L: Differential induction of interleukin-10 and interleukin-12 in den- dritic cells by microbial Toll-like receptor activators and skewing of T-cell cytokine profiles. Infect Immun 2003;71:3337-3342.
  358. Schnare M, Barton GM, Holt AC, et al: Toll-like receptors control activation of adaptive immune responses. Nat Immunol 2001;2:947-950.
  359. Bowie A, O'Neill LA: The interleukin-1 receptor/Toll-like receptor superfamily: signal genera- tors for pro-inflammatory interleukins and microbial products. J Leukoc Biol 2000;67:508-514.
  360. Re F, Strominger JL: Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. J Biol Chem 2001;276:37692-37699.
  361. Triantafilou M, Triantafilou K: Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends Immunol 2002;23:301-304.
  362. Akira S, Takeda K: Toll-like receptor signalling. Nat Rev Immunol 2004;4:499-511.
  363. Doyle S, Vaidya S, O'Connell R, et al: IRF3 mediates a TLR3/TLR4-specific antiviral gene pro- gram. Immunity 2002;17:251-263.
  364. Gautier G, Humbert M, Deauvieau F, et al: A type I interferon autocrine-paracrine loop is involved in Toll-like receptor-induced interleukin-12p70 secretion by dendritic cells. J Exp Med 2005;201: 1435-1446.
  365. Kaplan HJ, Streilein JW, Stevens TR: Transplantation immunology of the anterior chamber of the eye. II. Immune response to allogeneic cells. J Immunol 1975;115:805-810.
  366. Kaiser C, Ksander B, Streilein J: Inhibition of lymphocyte proliferation by aqueous humor. Reg Immunol 1989;2:42-49.
  367. Niederkorn JY, Benson JL, Mayhew E: Efferent blockade of delayed-type hypersensitivity responses in the anterior chamber of the eye. Reg Immunol 1991;3:349-354.
  368. Cousins SW, Trattler WB, Streilein JW: Immune privilege and suppression of immunogenic inflammation in the anterior chamber of the eye. Curr Eye Res 1991;10:287-297.
  369. Taylor AW, Streilein JW, Cousins SW: Identification of alpha-melanocyte stimulating hor- mone as a potential immunosuppressive factor in aqueous humor. Curr Eye Res 1992;11: 1199-1206.
  370. Nishida T, Taylor AW: Specific aqueous humor factors induce activation of regulatory T cells. Invest Ophthalmol Vis Sci 1999;40:2268-2274.
  371. Taylor AW: Immunoregulation of the ocular effector responses by soluble factors in aqueous humor. Reg Immunol 1994;6:52-57.
  372. Pasquale LR, Dorman-Pease ME, Lutty GA, Quigley HA, Jampel HD: Immunolocalization of TGF-␤1, TGF-1␤2, and TGF-2␤3 in the anterior segment of the human eye. Invest Ophthalmol Vis Sci 1993;34:23-30.
  373. Knisely TL, Bleicher PA, Vibbard CA, Granstein RD: Production of latent transforming growth factor-beta and other inhibitory factors by cultured murine iris and ciliary body cells. Curr Eye Res 1991;10:761-771.
  374. Wilbanks GA, Streilein JW: Fluids from immune privileged sites endow macrophages with the capacity to induce antigen-specific immune deviation via a mechanism involving transforming growth factor-beta. Eur J Immunol 1992;22:1031-1036.
  375. Takeuchi M, Kosiewicz MM, Alard P, Streilein JW: On the mechanisms by which transforming growth factor-␤2 alters antigen-presenting abilities of macrophages on T cell activation. Eur J Immunol 1997;27:1648-1656.
  376. Takeuchi M, Alard P, Streilein JW: TGF-␤ promotes immune deviation by altering accessory sig- nals of antigen-presenting cells. J Immunol 1998;160:1589-1597.
  377. Tsunawaki S, Sporn M, Ding A, Nathan C: Deactivation of macrophages by transforming growth factor-␤. Nature 1988;334:260-262.
  378. Chantry D, Turner M, Abney E, Feldmann M: Modulation of cytokine production by transforming growth factor-␤. J Immunol 1989;142:4295-4300.
  379. Bogdan C, Paik J, Vodovotz Y, Nathan C: Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-␤ and interleukin-10. J Biol Chem 1992;267: 23301-23308.
  380. Taylor AW, Alard P, Yee DG, Streilein JW: Aqueous humor induces transforming growth factor- beta (TGF-beta)-producing regulatory T-cells. Curr Eye Res 1997;16:900-908.
  381. Nunes I, Shapiro RL, Rifkin DB: Characterization of latent TGF-beta activation by murine peri- toneal macrophages. J Immunol 1995;155:1450-1459.
  382. Munger JS, Harpel JG, Gleizes PE, et al: Latent transforming growth factor-beta: structural fea- tures and mechanisms of activation. Kidney Int 1997;51:1376-1382.
  383. Taylor AW, Yee DG, Nishida T, Namba K: Neuropeptide regulation of immunity. The immunosup- pressive activity of alpha-melanocyte-stimulating hormone (alpha-MSH). Ann N Y Acad Sci 2000;917:239-247.
  384. Taylor A, Namba K: In vitro induction of CD25ϩ CD4ϩ regulatory T cells by the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH). Immunol Cell Biol 2001;79:358-367.
  385. Namba K, Kitaichi N, Nishida T, Taylor AW: Induction of regulatory T cells by the immunomodu- lating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-␤2. J Leukoc Biol 2002;72:946-952.
  386. Nakanishi S, Inoue A, Kita T, et al: Nucleotide sequence of cloned cDNA for bovine corticotropin- ␤-lipotropin precursor. Nature 1979;278:423-427.
  387. Lee TH, Lerner AB, Buettner-Janusch V: The isolation and structure of ␣-and ␤-melanocyte- stimulating hormones from monkey pituitary glands. J Biol Chem 1961;236:1390-1394.
  388. Watanabe T, Hiltz ME, Catania A, Lipton JM: Inhibition of IL-1␤-induced peripheral inflamma- tion by peripheral and central administration of analogs of the neuropeptide ␣-MSH. Brain Res Bull 1993;32:311-314.
  389. Martin LW, Catania A, Hiltz ME, Lipton JM: Neuropeptide alpha-MSH antagonizes IL-6-and TNF-induced fever. Peptides 1991;12:297-299.
  390. Lipton JM, Catania A: Anti-inflammatory actions of the neuroimmunomodulator ␣-MSH. Immunol Today 1997;18:140-145.
  391. Lipton JM: Modulation of host defense by the neuropeptide ␣-MSH. Yale J Biol Med 1990;63:173-182.
  392. Holdeman M, Khorram O, Samson WK, Lipton JM: Fever-specific changes in central MSH and CRF concentrations. Am J Physiol 1985;248:R125-R129.
  393. Star RA, Rajora N, Huang J, et al: Evidence of autocrine modulation of macrophage nitric oxide synthase by ␣-MSH. Proc Natl Acad Sci 1995;90:8856-8860.
  394. Rajora N, Ceriani G, Catania A, et al: ␣-MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line. J Leukoc Biol 1996;59:248-253.
  395. Chiao H, Foster S, Thomas R, Lipton J, Star RA: ␣-Melanocyte stimulating hormone reduces endotoxin-induced liver inflammation. J Clin Invest 1996;97:2038-2044.
  396. Ortego J, Wollmann G, Coca-Prados M: Differential regulation of gene expression of neurotensin and prohormone convertases PC1 and PC2 in the bovine ocular ciliary epithelium: possible impli- cations on neurotensin processing. Neurosci Lett 2002;333:49-53.
  397. O'Donohue TL, Dorsa DM: The opiomelanotropinergic neuronal and endocrine systems. Peptides 1982;3:353-395.
  398. Chakraborty AK, Funasaka Y, Slominski A, et al: Production and release of proopiomelanocortin (POMC) derived peptides by human melanocytes and keratinocytes in culture: regulation by ultra- violet B. Biochim Biophys Acta 1996;1313:130-138.
  399. Taylor AW, Streilein JW, Cousins SW: Alpha-melanocyte-stimulating hormone suppresses antigen- stimulated T cell production of gamma-interferon. Neuroimmunomodulation 1994;1:188-194.
  400. Nishida T, Miyata S, Itoh Y, et al: Anti-inflammatory effects of alpha-melanocyte-stimulating hor- mone against rat endotoxin-induced uveitis and the time course of inflammatory agents in aqueous humor. Int Immunopharmacol 2004;4:1059-1066.
  401. Shiratori K, Ohgami K, Ilieva IB, et al: Inhibition of endotoxin-induced uveitis and potentiation of cyclooxygenase-2 protein expression by alpha-melanocyte-stimulating hormone. Invest Ophthalmol Vis Sci 2004;45:159-164.
  402. Naveh N, Marshall J: Melanocortins are comparable to corticosteroids as inhibitors of traumatic ocular inflammation in rabbits. Graefes Arch Clin Exp Ophthalmol 2001;239:840-844. Taylor AW: The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages. J Neuroimmunol 2005;162:43-50.
  403. Taylor AW, Yee DG, Streilein JW: Suppression of nitric oxide generated by inflammatory macrophages by calcitonin gene-related peptide in aqueous humor. Invest Ophthalmol Vis Sci 1998;39:1372-1378.
  404. Taylor AW, Yee DG: Somatostatin is an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 2003;44:2644-2649.
  405. Taylor AW, Streilein JW, Cousins SW: Immunoreactive vasoactive intestinal peptide contributes to the immunosuppressive activity of normal aqueous humor. J Immunol 1994;153:1080-1086.
  406. Muscettola M, Grasso G: Somatostatin and vasoactive intestinal peptide reduce interferon gamma production by human peripheral blood mononuclear cells. Immunobiology 1990;180:419-430.
  407. O'Dorisio MS, Wood CL, O'Dorisio TM: Vasoactive intestinal peptide and neuropeptide modula- tion of the immune response. J Immunol 1985;135:792s-796s.
  408. Ottaway CA: Vasoactive intestinal peptide as a modulator of lymphocyte and immune function. Ann N Y Acad Sci 1988;527:486-500.
  409. Stanisz AM, Scicchitano R, Bienenstock J: The role of vasoactive intestinal peptide and other neu- ropeptides in the regulation of the immune response in vitro and in vivo. Ann N Y Acad Sci 1988;527:478-485.
  410. Tseng J, O'Dorisio MS: Mechanism of vasoactive intestinal peptide (VIP)-mediated immunoreg- ulation; in Goetzl EJ, Spector NH (eds): Neuroimmune Networks: Physiology and Diseases. New York, Liss, 1989, pp 105-111.
  411. Boudard F, Bastide M: Inhibition of mouse T-cell proliferation by CGRP and VIP: effects of these neuropeptides on IL-2 production and cAMP synthesis. J Neurosci Res 1991;29:29-41.
  412. Ganea D, Sun L: Vasoactive intestinal peptide downregulates the expression of IL-2 but not of INF-␥ from stimulated murine T lymphocytes. J Neuroimmunol 1993;47:147-158.
  413. Uddman R, Alumets J, Ehinger B, et al: Vasoactive intestinal peptide nerves in ocular and orbital structures of the cat. Invest Ophthalmol Vis Sci 1980;19:878-885.
  414. Terenghi G, Polak JM, Ghatei MA, et al: Distribution and origin of calcitonin gene-related peptide (CGRP) immunoreactivity in the sensory innervation of the mammalian eye. J Comp Neurol 1985;233:506-516.
  415. Wright LL, Luebke JI: Somatostatin-, vasoactive intestinal polypeptide-and neuropeptide Y-like immunoreactivity in eye-and submandibular gland-projecting sympathetic neurons. Brain Res 1989;494:267-275.
  416. Vasilaki A, Papadaki T, Notas G, et al: Effect of somatostatin on nitric oxide production in human retinal pigment epithelium cell cultures. Invest Ophthalmol Vis Sci 2004;45:1499-1506.
  417. Cristiani R, Petrucci C, Dal Monte M, Bagnoli P: Somatostatin (SRIF) and SRIF receptors in the mouse retina. Brain Res 2002;936:1-14.
  418. Larsen JN, Bersani M, Olcese J, Holst JJ, Moller M: Somatostatin and prosomatostatin in the retina of the rat: an immunohistochemical, in-situ hybridization, and chromatographic study. Vis Neurosci 1990;5:441-452.
  419. Gaur VP, Yamaguchi K, Turner JE: Somatostatin in rat retina: localization by in situ hybridization histochemistry and immunocytochemistry. Tohoku J Exp Med 1990;162:121-126.
  420. Yamaguchi K, Gaur VP, Spira AW, Turner JE: Cellular localization of somatostatin mRNA in rat retina. Neuropeptides 1990;17:13-16.
  421. Ottaway CA: Selective effects of vasoactive intestinal peptide on the mitogenic response of murine T cells. Immunology 1987;62:291-297.
  422. Caspi RR, Sun B, Agarwal RK, et al: T cell mechanisms in experimental autoimmune uveoretini- tis: susceptibility is a function of the cytokine response profile. Eye 1997;11(pt 2):209-212.
  423. Kitaichi N, Namba K, Taylor AW: Inducible immune regulation following autoimmune disease in the immune-privileged eye. J Leukoc Biol 2005;77:496-502.
  424. Lin HH, Faunce DE, Stacey M, et al: The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. J Exp Med 2005;201: 1615-1625.
  425. D'Orazio TJ, Mayhew E, Niederkorn JY: Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1. J Immunol 2001;166:26-32.
  426. Wilbanks GA, Streilein JW: Characterization of suppressor cells in anterior chamber-associated immune deviation (ACAID) induced by soluble antigen. Evidence of two functionally and pheno- typically distinct T-suppressor cell populations. Immunology 1990;71:383-389.
  427. Taylor AW, Kitaichi N, Biros DJ: Melanocortin 5 receptor and ocular immunity. Cell Mol Biol (Noisy-le-grand) 2006;52:53-59.
  428. Song XY, Gu M, Jin WW, Klinman DM, Wahl SM: Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model. J Clin Invest 1998;101:2615-2621.
  429. Croxford JL, Triantaphyllopoulos K, Podhajcer OL, et al: Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the cen- tral nervous system. J Immunol 1998;160:5181-5187.
  430. Brauner R, Nonoyama M, Laks H, et al: Intracoronary adenovirus-mediated transfer of immunosup- pressive cytokine genes prolongs allograft survival. J Thorac Cardiovasc Surg 1997;114:923-933.
  431. Wintzen M, Gilchrest BA: Proopiomelanocortin, its derived peptides, and the skin. J Invest Dermatol 1996;106:3-10.
  432. Thody AJ, Ridley K, Penny RJ, et al: MSH peptides are present in mammalian skin. Peptides 1983;4: 813-816. Dr. Andrew W. Taylor Schepens Eye Research Institute, Harvard Medical School
  433. Staniford Street Boston, MA 02114 (USA)
  434. Tel. ϩ1 617 912 7452, Fax ϩ1 617 912 0137, E-Mail awtaylor@vision.eri.harvard.edu Niederkorn JY, Kaplan HJ (eds): Immune Response and the Eye. Chem Immunol Allergy. Basel, Karger, 2007, vol 92, pp 86-93
  435. Jiang LQ, Jorquera M, Streilein JW: Subretinal space and vitreous cavity as immunologically priv- ileged sites for retinal allografts. Invest Ophthalmol Vis Sci 1993;34:3347-3354.
  436. Jiang LQ, Jorquera M, Streilein JW: Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts. Exp Eye Res 1994;58:719-728.
  437. Jiang LQ, Streilein JW: Immune privilege extended to allogeneic tumor cells in the vitreous cav- ity. Invest Ophthalmol Vis Sci 1991;32:224-228.
  438. Sonoda KH, Sakamoto T, Qiao H, Hisatomi T, Oshima T, Tsutsumi-Miyahara C, Exley M, Balk SP , Taniguchi M, Ishibashi T: The analysis of systemic tolerance elicited by antigen inoculation into the vitreous cavity: vitreous cavity-associated immune deviation. Immunology 2005;116: 390-399.
  439. Wenkel H, Chen PW , Ksander BR, Streilein JW: Immune privilege is extended, then withdrawn, from allogeneic tumor cell grafts placed in the subretinal space. Invest Ophthalmol Vis Sci 1999;40:3202-3208.
  440. Wenkel H, Streilein JW: Analysis of immune deviation elicited by antigens injected into the sub- retinal space. Invest Ophthalmol Vis Sci 1998;39:1823-1834.
  441. Klein RJ, Zeiss C, Chew EY , Tsai JY , Sackler RS, Haynes C, Henning AK, SanGiovanni JP , Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J: Complement factor H polymorphism in age-related macular degeneration. Science 2005;308:385-389.
  442. Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA: Complement factor H polymorphism and age-related macular degeneration. Science 2005;308:421-424.
  443. 9 Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P , Spencer KL, Kwan SY , Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, Pericak-Vance MA: Complement factor H variant increases the risk of age-related macular degeneration. Science 2005;308:419-421.
  444. Anderson DH, Mullins RF, Hageman GS, Johnson LV: A role for local inflammation in the forma- tion of drusen in the aging eye. Am J Ophthalmol 2002;134:411-431.
  445. Knisely TL, Bleicher PA, Vibbard CA, Granstein RD: Production of latent transforming growth factor-beta and other inhibitory factors by cultured murine iris and ciliary body cells. Curr Eye Res 1991;10:761-771.
  446. Streilein JW, Bradley D: Analysis of immunosuppressive properties of iris and ciliary body cells and their secretory products. Invest Ophthalmol Vis Sci 1991;32:2700-2710.
  447. Griffith TS, Ferguson TA: The role of FasL-induced apoptosis in immune privilege. Immunol Today 1997;18:240-244.
  448. Jorgensen A, Wiencke AK, la Cour M, Kaestel CG, Madsen HO, Hamann S, Lui GM, Scherfig E, Prause JU, Svejgaard A, Odum N, Nissen MH, Ropke C: Human retinal pigment epithelial cell- induced apoptosis in activated T cells. Invest Ophthalmol Vis Sci 1998;39:1590-1599.
  449. Yoshida M, Takeuchi M, Streilein JW: Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 1. Inhibition of T-cell activation in vitro by direct cell-to-cell contact. Invest Ophthalmol Vis Sci 2000;41:811-821.
  450. Yoshida M, Kezuka T, Streilein JW: Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 2. Generation of TGF-beta-producing regulatory T cells. Invest Ophthalmol Vis Sci 2000;41:3862-3870.
  451. Ishida K, Panjwani N, Cao Z, Streilein JW: Participation of pigment epithelium in ocular immune privilege. 3. Epithelia cultured from iris, ciliary body, and retina suppress T-cell activation by par- tially non-overlapping mechanisms. Ocul Immunol Inflamm 2003;11:91-105.
  452. Zamiri P, Masli S, Kitaichi N, Taylor AW, Streilein JW: Thrombospondin plays a vital role in the immune privilege of the eye. Invest Ophthalmol Vis Sci 2005;46:908-919.
  453. Tanihara H, Yoshida M, Matsumoto M, Yoshimura N: Identification of transforming growth factor-beta expressed in cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 1993;34:413-419.
  454. Obata H, Kaji Y, Yamada H, Kato M, Tsuru T, Yamashita H: Expression of transforming growth factor-beta superfamily receptors in rat eyes. Acta Ophthalmol Scand 1999;77:151-156. Lawler J: The functions of thrombospondin-1 and -2. Curr Opin Cell Biol 2000;12:634-640.
  455. Murphy-Ullrich JE, Poczatek M: Activation of latent TGF-beta by thrombospondin-1: mecha- nisms and physiology. Cytokine Growth Factor Rev 2000;11:59-69.
  456. Miyajima-Uchida H, Hayashi H, Beppu R, Kuroki M, Fukami M, Arakawa F, Tomita Y, Kuroki M, Oshima K: Production and accumulation of thrombospondin-1 in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 2000;41: 561-567.
  457. Elner SG: Human retinal pigment epithelial lysis of extracellular matrix: functional urokinase plasminogen activator receptor, collagenase, and elastase. Trans Am Ophthalmol Soc 2002;100: 273-299. Patel YC: Somatostatin and its receptor family. Front Neuroendocrinol 1999;20:157-198.
  458. Blum AM, Metwali A, Mathew RC, Cook G, Elliott D, Weinstock JV: Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion. J Immunol 1992;149:3621-3626.
  459. Klisovic DD, O'Dorisio MS, Katz SE, Sall JW, Balster D, O'Dorisio TM, Craig E, Lubow M: Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemi- cal study. Invest Ophthalmol Vis Sci 2001;42: 2193-2201.
  460. Zamiri P, Masli S, Streilein JW, Taylor AW: Pigment epithelial growth factor suppresses inflam- mation by modulating macrophage activation. Invest Ophthalmol Vis Sci 2006;47:3912-3918.
  461. Taylor AW, Yee DG: Somatostatin is an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 2003;44:2644-2649.
  462. Karakousis PC, John SK, Behling KC, Surace EM, Smith JE, Hendrickson A, Tang WX, Bennett J, Milam AH: Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues. Mol Vis 2001;7:154-163.
  463. Cohen J, Sugita Y, Chader GJ, Schwartz JP: Recombinant forms of the neurotrophic factor pig- ment epithelium-derived factor activate cellular metabolism and inhibit proliferation of the RAW macrophage cell line. Neuroimmunomodulation 2000;7:51-58.
  464. Sugita S, Streilein JW: Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2003;198: 161-171.
  465. Greenwald RJ, Boussiotis VA, Lorsbach RB, Abbas AK, Sharpe AH: CTLA-4 regulates induction of anergy in vivo. Immunity 2001;14:145-155.
  466. Scheipers P, Reiser H: Fas-independent death of activated CD4 ϩ T lymphocytes induced by CTLA-4 crosslinking. Proc Natl Acad Sci USA 1998;95:10083-10088.
  467. Levings MK, Sangregorio R, Sartirana C, et al: Human CD25ϩCD4ϩ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T reg- ulatory cells. J Exp Med 2002;196:1335-1346.
  468. Read S, Malmstrom V, Powrie F: Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25 ϩ CD4 ϩ regulatory cells that control intestinal inflammation. J Exp Med 2000;192:295-302.
  469. Takahashi T, Tagami T, Yamazaki S, et al: Immunologic self-tolerance maintained by CD25 ϩ CD4 ϩ regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2000;192:303-310.
  470. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189-1192.
  471. Lee HO, Herndon JM, Barreiro R, Griffith TS, Ferguson TA: TRAIL: a mechanism of tumor sur- veillance in an immune privileged site. J Immunol 2002;169:4739-4744.
  472. Wang S, Boonman ZF, Li HC, et al: Role of TRAIL and IFN-gamma in CD4ϩ T cell-dependent tumor rejection in the anterior chamber of the eye. J Immunol 2003;171:2789-2796.
  473. Mieziewska K: The interphotoreceptor matrix, a space in sight. Microsc Res Tech 1996;35: 463-471.
  474. Wenkel H, Streilein JW: Evidence that retinal pigment epithelium functions as an immune-privileged tissue. Invest Ophthalmol Vis Sci 2000;41:3467-3473.
  475. Streilein JW, Ma N, Wenkel H, Ng TF, Zamiri P: Immunobiology and privilege of neuronal retina and pigment epithelium transplants. Vision Res 2002;42:487-495.
  476. Kaplan HJ, Tezel TH, Berger AS, Del Priore LV: Retinal transplantation; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 207-219.
  477. Ashton N: Bowman lecture. The blood-retinal barrier and vaso-glial relationships in retinal dis- ease. Trans Ophthalmol Soc UK 1965;85:199-230.
  478. Marmor MF: Mechanisms of fluid accumulation in retinal edema. Doc Ophthalmol 1999;97: 239-249.
  479. Caspi RR, Roberge FG: Glial cells as suppressor cells: characterization of the inhibitory function. J Autoimmun 1989;2:709-722.
  480. Liversidge J, McKay D, Mullen G, Forrester JV: Retinal pigment epithelial cells modulate lym- phocyte function at the blood-retina barrier by autocrine PGE2 and membrane-bound mecha- nisms. Cell Immunol 1993;149:315-330.
  481. Dr. Parisa Zamiri Advanced Microscopy Program Wellman Center for Photomedicine CPZN8238, 185 Cambridge Street Boston, MA 02114 (USA)
  482. Tel. ϩ1 617 726 4236, Fax ϩ1 617 724 2075, E-Mail pzamiri@partners.org References
  483. Burns J, Rosenzweig A, Zweiman B, et al: Isolation of myelin basic protein-reactive T -cell lines from normal human blood. Cell Immunol 1983;81:435-440.
  484. Schlüsener HJ, Wekerle H: Autoaggressive T lymphocyte lines recognizing the encephalitogenic region of myelin basic protein: in vitro selection from unprimed rat T lymphocyte populations. J Immunol 1985;135:3128-3133.
  485. Massa PT, ter Meulen V, Fontana A: Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 1987;84:4219-4223.
  486. Chung IY , Norris JG, Benveniste EN: Differential tumor necrosis factor ␣ expression by astro- cytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains. J Exp Med 1991;173:801-811.
  487. Shao H, Sun SL, Kaplan HJ, et al: Characterization of rat CD8ϩ uveitogenic T cells specific for interphotoreceptor retinal-binding protein 1177-1191. J Immunol 2004;173:2849-2854.
  488. Donoso LA, Merryman CF , Sery T, et al: Human interstitial retinoid binding protein: a potent uveitopathogenic agent for the induction of experimental autoimmune uveitis. J Immunol 1989;143: 79-83.
  489. Chan CC, Nussenblatt RB, Wiggert B, et al: Immunohistochemical analysis of experimental autoimmune uveoretinitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) in the rat. Immunol Invest 1987;16:63-74.
  490. Caspi RR: Experimental autoimmune uveoretinitis -rat and mouse; in Cohen IR (ed): Animal Models for Autoimmune Diseases: A Guidebook. New York, Academic Press, 1994, p 57. Silver PB, Rizzo L V , Chan CC, et al: Identification of a major pathogenic epitope in the human IRBP molecule recognized by mice of the H-2r haplotype. Invest Ophthalmol Vis Sci 1995;36: 946-954.
  491. Shao H, Peng Y, Liao T, et al: A shared epitope of the interphotoreceptor retinoid-binding protein recognized by the CD4ϩ and CD8ϩ autoreactive T cells. J Immunol 2005;175:1851-1857.
  492. Shao H, Liao T, Ke Y, et al: Severe chronic experimental autoimmune uveitis (EAU) of the C57BL/6 mouse induced by adoptive transfer of IRBP1-20-specific T cells. Exp Eye Res 2006;82:323-331.
  493. Shao H, Song L, Sun SL, et al: Conversion of monophasic to recurrent autoimmune disease by autoreactive T cell subsets. J Immunol 2003;171:5624-5630.
  494. Sun D, Hu X, Le J, et al: Characterization of brain-isolated rat encephalitogenic T cell lines. Eur J Immunol 1994;24:1359-1364.
  495. Sun D, Le J, Coleclough C: Diverse T cell receptor ␤ chain usage by rat encephalitogenic T cells reactive to residues 68-88 of myelin basic protein. Eur J Immunol 1993;23:494-498.
  496. Sun D, Gold DP, Smith L, et al: Characterization of rat encephalitogenic T cells bearing non-V b 8 T cell receptors. Eur J Immunol 1992;22:591-594.
  497. Shao H, Fu YX, Song L, et al: LTbR-Ig treatment blocks actively induced, but not adoptively trans- ferred, uveitis in Lewis rats. Eur J Immunol 2003;33:1743.
  498. Shao H, Fu Y, Liao T, et al: Anti-CD137 mAb treatment inhibits experimental autoimmune uveitis by limiting expansion and increasing apoptotic death of uveitogenic T cells. Invest Ophthalmol Vis Sci 2005;46:596-603.
  499. Sun D, Hu X, Shah R, et al: Production of tumor necrosis factor-␣ as a result of glia-T-cell inter- action correlates with the pathogenic activity of myelin basic protein-reactive T cells in experi- mental autoimmune encephalomyelitis. J Neurosci Res 1996;45:400-409.
  500. Sun D, Coleclough C, Whitaker JN: Nonactivated astrocytes downregulate T cell receptor expres- sion and reduce antigen-specific proliferation and cytokine production of myelin basic protein (MBP)-reactive T cells. J Neuroimmunol 1997;78:69-78.
  501. Sun D, Hu XZ, Liu XH, et al: Expression of chemokine genes in rat glial cells: the effect of myelin basic protein-reactive encephalitogenic T cells. J Neurosci Res 1997;48:192-200.
  502. Olsson T, Sun J, Hillert J, et al: Increased numbers of T cells recognizing multiple myelin basic protein epitopes in multiple sclerosis. Eur J Immunol 1992;22:1083-1087.
  503. Sun D, Wilson DB, Cao L, et al: The role of regulatory T cells in Lewis rats resistant to EAE. J Neuroimmunol 1998;81:177-183.
  504. Werdelin O, McCluskey RT: The nature and the specificity of mononuclear cells in experimental autoimmune inflammations and the mechanisms leading to their accumulation. J Exp Med 1971;133:1242-1263.
  505. Zinn KM, Benjamin-Henkind JV: Anatomy of the human retinal pigment epithelium; in Zinn KM, Marmor MF (eds): The retinal pigment epithelium. Cambridge, Harvard University Press, 2002, pp 3-31.
  506. Farrokh-Siar L, Rezai KA, Semnani RT, et al: Human fetal retinal pigment epithelium suppresses the activation of CD4 ϩ and CD8 ϩ T-cells. Graefes Arch Clin Exp Ophthalmol 1999;237:934-939.
  507. Faure V, Courtois Y, Goureau O: Inhibition of inducible nitric oxide synthase expression by TNF ␣ and ␤ in bovine retinal pigmented epithelial cells. J Biol Chem 1997;272:32169-32175.
  508. Holtkamp GM, Kijlstra A, Peek R, et al: Retinal pigment epithelium-immune system interactions: cytokine production and cytokine-induced changes. Prog Retin Eye Res 2001;20:29-48.
  509. Liversidge J, Forrester JV: Antigen processing and presentation in the eye: a review. Curr Eye Res 1992;11:49-58.
  510. Griffith TS, Brunner T, Fletcher SM, et al: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189-1192.
  511. Griffith TS, Ferguson TA: The role of FasL-induced apoptosis in immune privilege. Immunol Today 1997;18:240-244.
  512. Jorgensen A, Wiencke AK, la Cour M, et al: Human retinal pigment epithelial cell-induced apop- tosis in activated T cells. Invest Ophthalmol Vis Sci 1998;39:1590-1599.
  513. Crane IJ, Kuppner MC, Mckillop-Smith S, et al: Cytokine regulation of RANTES production by human retinal pigment epithelial cells. Cell Immunol 1998;184:37-44.
  514. Crane IJ, Wallace CA, Mckillop-Smith S, et al: Control of chemokine production at the blood- retina barrier. Immunology 2000;101:426-433.
  515. Devine L, Lightman S, Greenwood J: Lymphocyte migration across the anterior and posterior blood-retinal barrier in vitro. Cell Immunol 1996;168:267-275.
  516. Jaffe GJ, Van Le L, Valea F, et al: Expression of interleukin-1 alpha, interleukin-1 beta, and an interleukin-1 receptor antagonist in human retinal pigment epithelial cells. Exp Eye Res 1992;55:325-335.
  517. Kumaki N, Anderson DM, Cosman D, et al: Expression of interleukin-15 and its receptor by human fetal retinal pigment epithelial cells. Curr Eye Res 1996;15:876-882.
  518. Liversidge J, Grabowski P, Ralston S, et al: Rat retinal pigment epithelial cells express an inducible form of nitric oxide synthase and produce nitric oxide in response to inflammatory cytokines and activated T cells. Immunology 1994;83:404-409.
  519. Hamel CP, Detrick B, Hooks JJ: Evaluation of Ia expression in rat ocular tissues following inocu- lation with interferon-gamma. Exp Eye Res 1990;50:173-182.
  520. Osusky R, Dorio RJ, Arora YK, et al: MHC class II positive retinal pigment epithelial (RPE) cells can function as antigen-presenting cells for microbial superantigen. Ocul Immunol Inflamm 1997;5:43-50.
  521. Percopo CM, Hooks JJ, Shinohara T, et al: Cytokine-mediated activation of a neuronal retinal resident cell provokes antigen presentation. J Immunol 1990;145:4101-4107.
  522. Zinkernagel R, Doherty PC: H-2-compatibility requirement for T cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus: different cytotoxic T cell specificities are associated with structures from H-2K or H-2D. J Exp Med 1975;141:1427-1436.
  523. Wong GMW, Bartlett PF, Clark-Lewis I, et al: Inducible expression of H-2 and Ia antigens on brain cells. Nature 1984;310:688-691.
  524. Traugott U, Scheinberg LC, Raine CS: On the presence of Ia-positive endothelial cells and astro- cytes in multiple sclerosis lesions and its relevance to antigen presentation. J Neuroimmunol 1985;8:1.
  525. Sun D, Enzmann V, Lei S, et al: Retinal pigment epithelial cells activate uveitogenic T cells when they express high levels of MHC class II molecules, but inhibit T cell activation when they express restricted levels. J Neuroimmunol 2003;144:1-8.
  526. Benson MT, Shepherd L, Cottam D, et al: The expression of class I major histocompatibility anti- gens by human retinal pigment epithelium in vitro. Graefes Arch Clin Exp Ophthalmol 1992;230:184-187.
  527. Detrick B, Newsome DA, Percopo CM, et al: Class II antigen expression and gamma interferon modulation of monocytes and retinal pigment epithelial cells from patients with retinitis pigmen- tosa. Clin Immunol Immunopathol 1985;36:201-211.
  528. de KY, Naud MC, Bellot J, et al: Differential tumor necrosis factor expression by resident retinal cells from experimental uveitis-susceptible and -resistant rat strains. J Neuroimmunol 1994;55: 1-9. Schwartz RH: Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 1992;71:1065-1068.
  529. Jenkins MK, Schwartz R: Antigen presentation by chemically modified splenocytes induces anti- gen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med 1987;165:302-310.
  530. Cao WX, Tykodi SS, Esser MT, et al: Partial activation of CD8 ϩ T cells by a self-derived peptide. Nature 1995;378:295-298.
  531. Evavold BD, Allen PM: Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science 1991;252:1308-1310.
  532. Sloan-Lancaster J, Shaw AS, Rothbard JB, et al: Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. Cell 1994;79:913-922.
  533. Sousa CRE, Levine EH, Germain RN: Partial signaling by CD8 ϩ T cells in response to antagonist ligands. J Exp Med 1996;184:149-157.
  534. Orihuela M, Margulies DH, Yokoyama WM: The natural killer cell receptor Ly-49A recognizes a peptide-induced conformational determinant on its major histocompatibility complex class I lig- and. Proc Natl Acad Sci USA 1996;93:11792-11797.
  535. Shao H, Van Kaer L, Sun SL, et al: Infiltration of the inflamed eye by NKT cells in a rat model of experimental autoimmune uveitis. J Autoimmun 2003;21:37-45.
  536. Sun D, Coleclough C, Hu X: Heterogeneity of rat encephalitogenic T cells elicited by variants of the MBP (68-88) peptide. Eur J Immunol 1995;25:1687-1692.
  537. Sun D, Hu X, Shah R, et al: The pattern of cytokine gene expression induced in rat T cells specific for myelin basic protein depends on the type and quality of antigenic stimulus. Cell Immunol 1995;166:1-8.
  538. Sun D, Le J, Yang S, et al: Major role of antigen-presenting cells in the response of rat encephalito- genic T cells to myelin basic proteins. J Immunol 1993;151:111-118.
  539. Tabi Z, McCombe PA, Pender MP: Apoptotic elimination of Vb8.2 ϩ cells from the central nervous system during recovery from experimental autoimmune encephalomyelitis induced by the passive transfer of Vb8.2 ϩ encephalitogenic T cells. Eur J Immunol 1994;24:2609-2617.
  540. Pender M, McCombe PA, Yoong G, et al: Apoptosis of ␣␤ T lymphocytes in the nervous system in experimental autoimmune encephalomyelitis: its possible implications for recovery and acquired tolerance. J Autoimmun 1992;5:401-410.
  541. Wekerle H, Linington C, Lassmann H, et al: Cellular immune reactivity within the CNS. Trends Neurosci 1986;9:271-277.
  542. Sun D, Wekerle H: Ia-restricted encephalitogenic T lymphocytes mediating EAE lyse autoantigen- presenting astrocytes. Nature 1986;320:70-72.
  543. Kawakami N, Odoardi F, Ziemssen T, et al: Autoimmune CD4ϩ T cell memory: lifelong persis- tence of encephalitogenic T cell clones in healthy immune repertoires. J Immunol 2005;175: 69-81.
  544. Flugel A, Berkowicz T, Ritter T, et al: Migratory activity and functional changes of green fluores- cent effector cells before and during experimental autoimmune encephalomyelitis. Immunity 2001;14:547-560.
  545. Dr. Henry J. Kaplan Department of Ophthalmology and Visual Science, University of Louisville 301 East Muhammad Ali Boulevard Louisville, KY 40202 (USA) Tel. ϩ1 502 852 5466, Fax ϩ1 502 852 4595, E-Mail hank.kaplan@louisville.edu References
  546. Atkinson JP , Farries T: Separation of self from non-self in the complement system. Immunol Today 1987;8:212-215.
  547. Dempsey PW , Allison MED, Akkaraju S, Goodnow CC, Fearon DT: C3d of complement as a mol- ecular adjuvant: bridging innate and acquired immunity. Science 1996;271:348-350.
  548. Carroll MC: The complement system in regulation of adaptive immunity. Nat Immunol 2004;5: 981-986.
  549. Sohn JH, Bora PS, Suk HJ, Molina H, Kaplan HJ, Bora NS: Tolerance is dependent on comple- ment C3 fragment iC3b binding to antigen-presenting cells. Nat Med 2003;9:206-212.
  550. Streilein JW: Immunologic privilege of the eye. Springer Semin Immunopathol 1999;21:95-111.
  551. Mondino BJ, Rao H: Hemolytic complement activity in aqueous humor. Arch Ophthalmol 1983;101:465-468.
  552. Bora NS, Gobleman CL, Atkinson JP , Pepose JS, Kaplan HJ: Differential expression of the com- plement regulatory proteins in the human eye. Invest Ophthalmol Vis Sci 1993;34:3579-3584.
  553. Sohn JH, Kaplan HJ, Suk HJ, Bora PS, Bora NS: Complement regulatory activity of normal human intraocular fluid is mediated by MCP, DAF, and CD59. Invest Ophthalmol Vis Sci 2000;41: 4195-4202.
  554. Sohn JH, Kaplan HJ, Suk HJ, Bora PS, Bora NS: Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins. Invest Ophthalmol Vis Sci 2000;41:3492-3502.
  555. Mondino BJ, Glovsky MM, Ghekiere L: Activated complement in inflamed aqueous humor. Invest Ophthalmol Vis Sci 1984;25:871-873.
  556. Marak GE, Wacker WB, Rao NA, Jack R, Ward PA: Effects of complement depletion on experi- mental allergic uveitis. Ophthalmic Res 1979;11:97-107.
  557. Bora NS, Sohn JH, Kang SG, et al: Type I collagen is the autoantigen in experimental autoimmune anterior uveitis. J Immunol 2004;172:7086-7094.
  558. Javitt JC, Chiang YP: Preparing for managed competition. Utilization of ophthalmologic services varies by state. Arch Ophthalmol 1993;111:1469-1470.
  559. US Census Bureau: National population projections. I. Summary files. 2002, http://www. census.gov/population/www/projections/natsum-T3.html
  560. West SK: Looking forward to 20/20: a focus on the epidemiology of eye diseases. Epidemiol Rev 2000;22:64-70.
  561. Lee PP, Feldman ZW, Ostermann J, Brown DS, Sloan FA: Longitudinal prevalence of major eye diseases. Arch Ophthalmol 2003;121:1303-1310.
  562. Klein R, Klein BE, Moss SE: Relation of smoking to the incidence of age-related maculopathy. The Beaver Dam Eye Study. Am J Epidemiol 1998;147:103-110.
  563. Klein R, Klein BE, Tomany SC, Meuer SM, Huang GH: Ten-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 2002;109:1767-1779.
  564. Bressler NM, Munoz B, Maguire MG, et al: Five-year incidence and disappearance of drusen and retinal pigment epithelial abnormalities. Waterman study. Arch Ophthalmol 1995;113: 301-308. Wang JJ, Foran S, Smith W, Mitchell P: Risk of age-related macular degeneration in eyes with macular drusen or hyperpigmentation: the Blue Mountains Eye Study cohort. Arch Ophthalmol 2003;121:658-663.
  565. Bird AC, Bressler NM, Bressler SB, et al: An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol 1995;39:367-374.
  566. Friedman DS, O'Colmain BJ, Munoz B, et al: Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004;122:564-572.
  567. Klein R, Peto T, Bird A, Vannewkirk MR: The epidemiology of age-related macular degeneration. Am J Ophthalmol 2004;137:486-495.
  568. Marx J: Genetics. A clearer view of macular degeneration. Science 2006;311:1704-1705.
  569. Klein BE, Klein R, Lee KE, Moore EL, Danforth L: Risk of incident age-related eye diseases in people with an affected sibling: the Beaver Dam Eye Study. Am J Epidemiol 2001;154: 207-211.
  570. Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willett WC: The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels. Am J Epidemiol 1988;127:283-296.
  571. Bettman J, Fellows V, Chao P: The effect of cigarette smoking on the intraocular circulation. Arch Ophthalmol 1958;59:481-488.
  572. Friedmann E: Choroidal blood flow: pressure-flow relationships. Arch Ophthalmol 1970;83:95-99.
  573. Age-Related Eye Disease Study Research Group: A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report No. 8. Arch Ophthalmol 2001;119: 1417-1436.
  574. Macular Photocoagulation Study Group: Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Updated findings from two clinical trials. Arch Ophthalmol 1993;111:1200-1209.
  575. Macular Photocoagulation Study Group: Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1991;109:1220-1231.
  576. American Academy of Ophthalmology: Photodynamic therapy with verteporfin for age-related macular degeneration. Ophthalmology 2000;107:2314-2317.
  577. Tezel TH, Del Priore LV, Flowers BE, et al: Correlation between scanning laser ophthalmoscope microperimetry and anatomic abnormalities in patients with subfoveal neovascularization. Ophthalmology 1996;103:1829-1836.
  578. Moisseiev J, Alhalel A, Masuri R, Treister G: The impact of the macular photocoagulation study results on the treatment of exudative age-related macular degeneration. Arch Ophthalmol 1995;113:185-189.
  579. Sharma S, Brown GC, Brown MM, Hollands H, Shah GK: The cost-effectiveness of photody- namic therapy for fellow eyes with subfoveal choroidal neovascularization secondary to age- related macular degeneration. Ophthalmology 2001;108:2051-2059.
  580. Busbee BG, Brown MM, Brown GC, Sharma S: CME review: a cost-utility analysis of laser photocoagulation for extrafoveal choroidal neovascularization. Retina 2003;23:279-287, quiz 443-444.
  581. Poliner LS, Tornambe PE, Michelson PE, Heitzmann JG: Interferon alpha-2a for subfoveal neo- vascularization in age-related macular degeneration. Ophthalmology 1993;100:1417-1424.
  582. Ciulla TA, Danis RP, Klein SB, et al: Proton therapy for exudative age-related macular degenera- tion: a randomized, sham-controlled clinical trial. Am J Ophthalmol 2002;134:905-906.
  583. Rao PK, Thomas MA: Update on surgical removal of choroidal neovascularization. Curr Opin Ophthalmol 2000;11:180-185.
  584. Lai JC, Lapolice DJ, Stinnett SS, et al: Visual outcomes following macular translocation with 360- degree peripheral retinectomy. Arch Ophthalmol 2002;120:1317-1324.
  585. Krzystolik MG, Afshari MA, Adamis AP, et al: Prevention of experimental choroidal neovascular- ization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch Ophthalmol 2002;120:338-346.
  586. TES TESG: Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascular- ization secondary to age-related macular degeneration: phase II study results. Ophthalmology 2003;110:979-986.
  587. Penfold PL, Wen L, Madigan MC, Gillies MC, King NJ, Provis JM: Triamcinolone aceto- nide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration. Clin Exp Immunol 2000;121: 458-465.
  588. D'Amico DJ, Goldberg MF, Hudson H, et al: Anecortave acetate as monotherapy for the treatment of subfoveal lesions in patients with exudative age-related macular degeneration (AMD): interim (month 6) analysis of clinical safety and efficacy. Retina 2003;23:14-23.
  589. Rich RM, Rosenfeld PJ, Puliafito CA, Dubovy SR, Davis JL, Flynn HW, Gonzalez F, Feuer WJ, Lin RC, Lalwani GA, Nguyen JK, Dumar G: Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Retina 2006;26: 495-511.
  590. Spaide RF, Laud K, Fine HF, Klancnik JM, Meyerle CB, Yannuzzi LA, Sorenson J, Slakter J, Fisher Yl, Cooney MJ: Intravitreal bevacizumab treatment of choroidal neovascularization sec- ondary to age-related macular degeneration. Retina 2006;26:383-390.
  591. Rosenfeld PJ, Heier JS, Hantsbarger G, Shams N: Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration. Ophthalmology 2006;113:632.
  592. Mullins RF, Russell SR, Anderson DH, Hageman GS: Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 2000;14: 835-846.
  593. Anderson DH, Mullins RF, Hageman GS, Johnson LV: A role for local inflammation in the forma- tion of drusen in the aging eye. Am J Ophthalmol 2002;134:411-431.
  594. Bora PS, Sohn JH, Cruz JM, Jha P, et al: Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization. J Immunol 2005;174:491-497. Dr. Nalini S. Bora Department of Ophthalmology Pat and Willard Walker Eye Research Centre Jones Eye Insitute University of Arkansas for Medical Sciences 4301 West Markham, 523, Little Rock, AR 72205-7199 (USA) Tel. ϩ1 501 686 8293, Fax ϩ1 502 686 8316, E-Mail NBora@UAMS.edu References
  595. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:878-889.
  596. Matsubara M, Tanishima T: Wound-healing of corneal endothelium in monkey: an autoradio- graphic study. Jpn J Ophthalmol 1983;27:444-450.
  597. Streilein JW: Regional immunity and ocular immune privilege; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 11-38.
  598. Niederkorn J, Streilein JW , Shadduck JA: Deviant immune responses to allogeneic tumors injected intracamerally and subcutaneously in mice. Invest Ophthalmol Vis Sci 1980;20:355-363.
  599. Jiang LQ, Jorquera M, Streilein JW: Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts. Invest Ophthalmol Vis Sci 1993;34:3347-3354.
  600. Wenkel H, Chen PW , Ksander BR, Streilein JW: Immune privilege is extended, then withdrawn, from allogeneic tumor cell grafts placed in the subretinal space. Invest Ophthalmol Vis Sci 1999;40:3203-3208.
  601. Medawar PB: Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue and to the anterior chamber of the eye. Br J Exp Pathol 1948;29:58-69.
  602. Morelli AE, Thomson AW: Dendritic cells: regulators of alloimmunity and opportunities for toler- ance induction. Immunol Rev 2003;196:125-146.
  603. 9 Banchereau J, Briere F, Caux C, Savoust J, Lebecque S, Lie YJ, Pulendran B, Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:761-811.
  604. Matzinger P: Tolerance, danger, and the extended family. Annu Rev Immunol 1994;12:991-1045.
  605. Matzinger P: An innate sense of danger (review). Semin Immunol 1996;10:399-415.
  606. Zhang-Hoover J, Finn P, Stein-Streilein J: Modulation of ovalbumin-induced airway inflammation and hyperreactivity by tolerogenic APC. J Immunol 2005;175:7117-7124.
  607. Faunce DE, Sonoda KH, Stein-Streilein J: MIP-2 recruits NKT cells to the spleen during tolerance induction. J Immunol 2001;166:313-321.
  608. Streilein JW, Stein-Streilein J, Head J: Regional specialization in antigen presentation; in: The Reticuloendothelial System. New York, Plenum, 1986, pp 37-93.
  609. Taylor AW, Yee DG, Streilein JW: Suppression of nitric oxide generated by inflammatory macrophages by calcitonin gene-related peptide in aqueous humor. Invest Ophthalmol Vis Sci 1998;39:1372-1378.
  610. Apte RS, Niederkorn JY: Isolation and characterization of a unique natural killer cell inhibitory factor present in the anterior chamber of the eye. J Immunol 1996;156:2667-2673.
  611. Streilein JW, Stein-Streilein J: Does innate immune privilege exist? J Leukoc Biol 2000;67:479-487.
  612. Cousins SW, McCabe MM, Danielpour D, Streilein JW: Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 1991;32:2201-2211.
  613. Streilein JW, Bradley D: Analysis of immunosuppressive properties of iris and ciliary body cells and their secretory products. Invest Ophthalmol Vis Sci 1991;32:2700-2710.
  614. Hara Y, Caspi RR, Wiggert B, Dorf M, Streilein JW: Analysis of an in vitro-generated signal that induces systemic immune deviation similar to that elicited by antigen injected into the anterior chamber of the eye. J Immunol 1992;149:1531-1538.
  615. Wilbanks GA, Streilein JW: Fluids from immune privileged sites endow macrophages with the capacity to induce antigen-specific immune deviation via a mechanism involving transforming growth factor-beta. Eur J Immunol 1992;22:1031-1036.
  616. Ohta K, Wiggert B, Yamagami S, Taylor AW, Streilein JW: Analysis of immunomodulatory activi- ties of aqueous humor from eyes of mice with experimental autoimmune uveitis. J Immunol 2000;164:1185-1192.
  617. Ohta K, Yamagami S, Taylor AW, Streilein JW: IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 2000;41:2591-2599.
  618. Mo JS, Streilein JW: Immune privilege persists in eyes with extreme inflammation induced by intravitreal LPS. Eur J Immunol 2001;31:3806-3815.
  619. Camelo S, Shanley A, Voon AS, McMenamin PG: The distribution of antigen in lymphoid tis- sues following its injection into the anterior chamber of the rat eye. J Immunol 2004;172: 5388-5395.
  620. Streilein JW, Niederkorn JY: Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J Exp Med 1981;153:1058-1067.
  621. Dullforce PA, Garman KL, Seitz GW, Fleischmann RJ, Crespo SM, Planck SR, Parker DC, Rosenbaum JT: APCs in the anterior uveal tract do not migrate to draining lymph nodes. J Immunol 2004;172:6701-6708.
  622. Franklin RM, Remus LE: Conjunctival-associated lymphoid tissue: evidence for a role in the secretory immune system. Invest Ophthalmol Vis Sci 1984;25:181-187.
  623. Zierhut M, Elson CO, Forrester JV, Kijlstra A, Kraehenbuhl JP, Sullivan DA: Mucosal immunol- ogy and the eye. Immunol Today 1998;19:148-150.
  624. Hamrah P, Huq SO, Liu Y, Zhang Q, Dana MR: Corneal immunity is mediated by heterogeneous population of antigen-presenting cells. J Leukoc Biol 2003;74:172-178.
  625. Cursiefen C, Schlotzer-Schrehardt U, Kuchle M, Sorokin L, Breiteneder-Geleff S, Alitalo K, Jackson D: Lymphatic vessels in vascularized human corneas: immunohistochemical investiga- tion using LYVE-1 and podoplanin. Invest Ophthalmol Vis Sci 2002;43:2127-2135.
  626. Wilbanks GA, Streilein JW: The differing patterns of antigen release and local retention following anterior chamber and intravenous inoculation of soluble antigen. Evidence that the eye acts as an antigen depot. Reg Immunol 1989;2:390-398.
  627. Streilein JW, Wilbanks GA: Evidence that anterior chamber and intravenous antigen injections have distinctly different systemic immune consequences. Ocular Immunol Today 1990, pp 255-258.
  628. Sonoda KH, Taniguchi M, Stein-Streilein J: Long-term survival of corneal allografts is dependent on intact CD1d-reactive NKT cells. J Immunol 2002;168:2028-2034.
  629. Wilbanks GA, Mammolenti M, Streilein J: Studies on the induction of anterior chamber-associated immune deviation (ACAID). II. Eye-derived cells participate in generating blood-borne signals that induce ACAID. J Immunol 1991;146:3018-3024.
  630. Wilbanks GA, Streilein JW: Studies on the induction of anterior chamber-associated immune deviation (ACAID). I. Evidence that an antigen-specific, ACAID-inducing, cell-associated signal exists in the peripheral blood. J Immunol 1991;146:2610-2617.
  631. Flugel C, Kinne RW, Streilein JW, Lutjen-Drecoll E: Distinctive distribution of HLA class II pre- senting and bone marrow derived cells in the anterior segment of human eyes. Curr Eye Res 1992;11:1173-1183.
  632. D'Orazio TJ, Niederkorn JY: A novel role for TGF-␤ and IL-10 in the induction of immune privi- lege. J Immunol 1996;160:2089-2098.
  633. Streilein JW: Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 2003;74:179-185.
  634. Faunce DE, Stein-Streilein J: NKT cell-derived RANTES recruits APCs and CD8 ϩ T cells to the spleen during the generation of regulatory T cells in tolerance. J Immunol 2002;169:31-38.
  635. Sonoda KH, Exley M, Snapper S, Balk S, Stein-Streilein J: CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site. J Exp Med 1999;190:1215-1225.
  636. Hara Y, Okamoto S, Rouse B, Streilein JW: Evidence that peritoneal exudate cells cultured with eye-derived fluids are the proximate antigen-presenting cells in immune deviation of the ocular type. J Immunol 1993;151:5162-5171.
  637. Kuchroo VK, Minami M, Diamond B, Dorf ME: Functional analysis of cloned macrophage hybridomas. VI. Differential ability to induce immunity or suppression. J Immunol 1988;141: 10-16.
  638. Masli S, Turpie B, Hecker KH, Streilein JW: Expression of thrombospondin in TGFß-treated APCs and its relevance to their immune deviation-promoting properties. J Immunol 2002;168: 2264-2273.
  639. Stein-Streilein J, Streilein JW: Anterior chamber associated immune deviation (ACAID); regula- tion, biological relevance, and implications for therapy. Int Rev Immunol 2002;21:123-152.
  640. Niederkorn JY, Mayhew E: Role of splenic B cells in the immune privilege of the anterior cham- ber of the eye. Eur J Immunol 1995;25:2783-2787.
  641. D'Orazio TJ, Niederkorn JY: Splenic B cells are required for tolerogenic antigen presentation in the induction of anterior chamber-associated immune deviation (ACAID). Immunology 1998;95: 47-55.
  642. Lantz O, Bendelac A: An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4 ϩ and CD4-8 Ϫ T cells in mice and humans. J Exp Med 1994;180:1097-1106.
  643. Bendelac A: Mouse NK1 ϩ T cells. Curr Opin Immunol 1995;7:367-374.
  644. Exley M, Garcia J, Balk SP, Porcelli S: Requirements for CD1d recognition by human invariant V␣24 ϩ CD4 Ϫ CD8 Ϫ T cells. J Exp Med 1997;186:109-120.
  645. Brutkiewicz RR, Bennink JR, Yewdell JW, Bendelac A: TAP-independent, ␤ 2 -microglobulin- dependent surface expression of functional mouse CD11. J Exp Med 1995;182:1913-1919.
  646. Joyce S, Woods AS, Yewdell JW, Bennink JR, De Silva AD, Boesteanu A, Balk SP, Cotter RJ, Brutkiewicz RR: Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. Science 1998;279:1541-1544.
  647. Nishimura T, Kitamura H, Iwakabe K, Yahata T, Ohta A, Sato M, Takeda K, Okumura K, Van Kaer L, Kawano T, Taniguchi M, Nakui M, Sekimoto M, Koda T: The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes. Int Immunol 2000;12:987-994.
  648. Gumperz JE, Miyake S, Yamamura T, Brenner MB: Functionally distinct subsets of CD1d- restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med 2002;195:625-636.
  649. Nakamura T, Sonoda KH, Faunce DE, Gumperz J, Yamamura T, Miyake S, Stein-Streilein J: CD4 ϩ NKT cells, but not conventional CD4 ϩ T cells, are required to generate efferent CD8 ϩ T regulatory cells following antigen inoculation in an immune privileged site. J Immunol 2003;171:1266-1271.
  650. Sonoda KH, Faunce DE, Taniguchi M, Exley M, Balk S, Stein-Streilein J: NKT cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance. J Immunol 2001;166:42-50.
  651. Sonoda KH, Stein-Streilein J: CD1d on antigen-transporting APC and splenic marginal zone B cells promotes NKT cell-dependent tolerance. Eur J Immunol 2002;32:848-857.
  652. Niederkorn JY, Chiang EY, Ungchusri T, Stroynowski I: Expression of a nonclassical MHC class Ib molecule in the eye. Transplantation 1999;68:1790-1799.
  653. D'Orazio TJ, Mayhew E, Niederkorn JY: Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1. J Immunol 2001;166:26-32.
  654. Niederkorn JY: Immune privilege in the anterior chamber of the eye. Crit Rev Immunol 2002;22: 13-46.
  655. Austyn JM, Gordon S: F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol 1981;11:805-815.
  656. McKnight AJ, Gordon S: EGF-TM7: a novel subfamily of seven-transmembrane-region leukocyte cell-surface molecules. Immunol Today 1996;17:283-287.
  657. McKnight AJ, Gordon S: The EGF-TM7 family: unusual structures at the leukocyte surface. J Leukoc Biol 1998;63:271-280.
  658. Hamann J, Vogel B, van Schijndel GM, van Lier RA: The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J Exp Med 1996;184:1185-1189.
  659. Gordon S, Lawson L, Rabinowitz S, Crocker PR, Morris L, Perry VH: Antigen markers of macrophage differentiation in murine tissues. Curr Top Microbiol Immunol 1992;181:1-37.
  660. Ezekowitz RAB, Austyn JM, Stahl PD, Gordon S: Surface properties of BCG-activated mouse macrophages. Reduced expression of mannose-specific endocytosis, Fc receptors, and antigen F4/80 accompanies induction of Ia. J Exp Med 1981;154:60-76.
  661. Ezekowitz RA, Gordon S: Down-regulation of mannosyl receptor-mediated endocytosis and anti- gen F4/80 in bacillus Calmette-Guérin-activated mouse macrophages. Role of T lymphocytes and lymphokines. J Exp Med 1982;155:1623-1637.
  662. Lin HH, Faunce DE, Stacey M, Terajewicz A, Nakamura T, Zhang-Hoover J, Kerley M, Mucenski ML, Gordon S, Stein-Streilein J: The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. J Exp Med 2005;201:1615-1625.
  663. Katagiri K, Zhang-Hoover J, Mo JS, Stein-Streilein J, Streilein JW: Using tolerance induced via the anterior chamber of the eye to inhibit Th2-dependent pulmonary pathology. J Immunol 2002;169:84-89.
  664. Chen Y, Inobe J, Weiner HL: Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4ϩ and CD8ϩ cells mediate active suppression. J Immunol 1995;155:910-916.
  665. Makala LHC, Reyes JCS, Nishikawa Y, Tsushima Y, Xuan X, Huang X, Battsetseg B, Matsuo T, Nagasawa H: Phenotype and function of murine discrete Peyer's patch macrophage derived- dendritic cells. J Vet Med Sci 2003;65:491-499.
  666. Ikarashi Y, Mikami R, Bendelac A, Terme M, Chaput N, Terada M, Tursz T, Angevin E, Lemonnier FA, Wakasugi H, Zitvogel L: Dendritic cell maturation overrules H-2D-mediated natural killer T (NKT) cell inhibition: critical role for B7 in CD1d-dependent NKT cell interferon gamma pro- duction. J Exp Med 2001;194:1179-1186.
  667. Maeda M, Lohwasser S, Yamamura T, Takei F: Regulation of NKT cells by Ly49: analysis of pri- mary NKT cells and generation of NKT cell line. J Immunol 2001;167:4180-4186.
  668. Skold M, Cardell S: Differential regulation of Ly49 expression on CD4ϩ and CD4-CD8- (double negative) NK1.1ϩ T cells. Eur J Immunol 2000;30:2488-2496.
  669. Held W, Cado D, Raulet DH: Transgenic expression of the Ly49A natural killer cell receptor con- fers class I major histocompatibility complex (MHC)-specific inhibition and prevents bone mar- row allograft rejection. J Exp Med 1996;184:2037-2041.
  670. Ortaldo JR, Winkler-Pickett R, Mason AT, Mason LH: The Ly-49 family: regulation of cytotoxic- ity and cytokine production in murine CD3ϩ cells. J Immunol 1998;160:1158-1165.
  671. Asea A, Stein-Streilein J: Signalling through NK1.1 triggers NK cells to die but induces NKT cells to produce interleukin-4. Immunology 1998;93:296-305.
  672. Wenkel H, Streilein JW, Young MJ: Systemic immune deviation in the brain that does not depend on the integrity of the blood-brain barrier. J Immunol 2000;164:5125-5131.
  673. Terabe M, Matsui S, Noben-Trauth N, Chen H, Watson C, Donaldson DD, Carbone DP, Paul WE, Berzofsky JA: NKT cell mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 2000;1:515-520.
  674. Nakamura T, Terajewicz A, Stein-Streilein J: Mechanisms of peripheral tolerance following intra- cameral inoculation are independent of IL-13 or STAT6. J Immunol 2005;175:2643-2646. Dr. Joan Stein-Streilein Schepens Eye Research Institute, Harvard School of Medicine 20 Staniford Street Boston, MA 02114 (USA) Tel. ϩ1 617 912 7494, Fax ϩ1 617 912 0105, E-Mail jstein@vision.eri.harvard.edu References
  675. Niederkorn J: Immune privilege of the eye; in Chan LS (ed): Animal Models of Human Inflammatory Skin Diseases. New York, CRC Press, 2004, p 564.
  676. Niederkorn JY: Immune privilege in the anterior chamber of the eye. Crit Rev Immunol 2002;22:13-46.
  677. Niederkorn JY: Immunology and immunomodulation of corneal transplantation. Int Rev Immunol 2002;21:173-196.
  678. Niederkorn JY: The immune privilege of corneal grafts. J Leukoc Biol 2003;74:167-171.
  679. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:879-889.
  680. Streilein JW: Immune privilege as the result of local tissue barriers and immunosuppressive microenvironments. Curr Opin Immunol 1993;5:428-432.
  681. Bora NS, Gobleman CL, Atkinson JP , Pepose JS, Kaplan HJ: Differential expression of the complement regulatory proteins in the human eye. Invest Ophthalmol Vis Sci 1993;34: 3579-3584.
  682. Goslings WR, Prodeus AP , Streilein JW , et al: A small molecular weight factor in aqueous humor acts on C1q to prevent antibody-dependent complement activation. Invest Ophthalmol Vis Sci 1998;39:989-995.
  683. Lass JH, Walter EI, Burris TE, et al: Expression of two molecular forms of the complement decay-accelerating factor in the eye and lacrimal gland. Invest Ophthalmol Vis Sci 1990;31: 1136-1148.
  684. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189-1192.
  685. Ciccone E, Pende D, Vitale M, et al: Self class I molecules protect normal cells from lysis medi- ated by autologous natural killer cells. Eur J Immunol 1994;24:1003-1006.
  686. Ljunggren HG, Karre K: In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today 1990;11:237-244.
  687. Le Discorde M, Moreau P, Sabatier P, Legeais JM, Carosella ED: Expression of HLA-G in human cornea, an immune-privileged tissue. Hum Immunol 2003;64:1039-1044.
  688. Niederkorn JY, Chiang EY, Ungchusri T, Stroynowski I: Expression of a nonclassical MHC class Ib molecule in the eye. Transplantation 1999;68:1790-1799.
  689. Carosella ED, Moreau P, Aractingi S, Rouas-Freiss N: HLA-G: a shield against inflammatory aggression. Trends Immunol 2001;22:553-555.
  690. Yoshida M, Kezuka T, Streilein JW: Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 2. Generation of TGF-beta-producing regulatory T cells. Invest Ophthalmol Vis Sci 2000;41:3862-3870.
  691. Taylor AW, Yee DG: Somatostatin is an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 2003;44:2644-2649.
  692. Gregerson DS, Dou C: Spontaneous induction of immunoregulation by an endogenous retinal antigen. Invest Ophthalmol Vis Sci 2002;43:2984-2991.
  693. Kezuka T, Streilein JW: Analysis of in vivo regulatory properties of T cells activated in vitro by TGF␤2-treated antigen presenting cells. Invest Ophthalmol Vis Sci 2000;41:1410-1421.
  694. Wilbanks GA, Streilein JW: Characterization of suppressor cells in anterior chamber-associated immune deviation (ACAID) induced by soluble antigen. Evidence of two functionally and pheno- typically distinct T-suppressor cell populations. Immunology 1990;71:383-389.
  695. Hara Y, Okamoto S, Rouse B, Streilein JW: Evidence that peritoneal exudate cells cultured with eye-derived fluids are the proximate antigen-presenting cells in immune deviation of the ocular type. J Immunol 1993;151:5162-5171.
  696. D'Orazio TJ, Niederkorn JY: Splenic B cells are required for tolerogenic antigen presentation in the induction of anterior chamber-associated immune deviation (ACAID). Immunology 1998;95:47-55.
  697. Niederkorn JY, Mayhew E: Role of splenic B cells in the immune privilege of the anterior cham- ber of the eye. Eur J Immunol 1995;25:2783-2787.
  698. Skelsey ME, Mayhew E, Niederkorn JY: Splenic B cells act as antigen presenting cells for the induction of anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci 2003;44:5242-5251.
  699. Skelsey ME, Mellon J, Niederkorn JY: Gamma delta T cells are needed for ocular immune privi- lege and corneal graft survival. J Immunol 2001;166:4327-4333.
  700. Xu Y, Kapp JA: Gamma delta T cells are critical for the induction of anterior chamber-associated immune deviation. Immunology 2001;104:142-148.
  701. Faunce DE, Stein-Streilein J: NKT cell-derived RANTES recruits APCs and CD8ϩ T cells to the spleen during the generation of regulatory T cells in tolerance. J Immunol 2002;169:31-38.
  702. Sonoda KH, Exley M, Snapper S, Balk SP, Stein-Streilein J: CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site. J Exp Med 1999;190:1215-1226.
  703. Wang Y, Goldschneider I, Foss D, et al: Direct thymic involvement in anterior chamber-associated immune deviation: evidence for a nondeletional mechanism of centrally induced tolerance to extrathymic antigens in adult mice. J Immunol 1997;158:2150-2155.
  704. Skelsey ME, Mayhew E, Niederkorn JY: CD25ϩ, interleukin-10-producing CD4ϩ T cells are required for suppressor cell production and immune privilege in the anterior chamber of the eye. Immunology 2003;110:18-29.
  705. Li XY, D'Orazio LT, Niederkorn JY: Role of Th1 and Th2 cells in anterior chamber-associated immune deviation. Immunology 1996;89:34-40.
  706. Kosiewicz MM, Streilein JW: Intraocular injection of class II-restricted peptide induces an unex- pected population of CD8 regulatory cells. J Immunol 1996;157:1905-1912.
  707. Shevach EM: CD4ϩ CD25ϩ suppressor T cells: more questions than answers. Nat Rev Immunol 2002;2:389-400.
  708. Maloy KJ, Powrie F: Regulatory T cells in the control of immune pathology. Nat Immunol 2001;2: 816-822.
  709. Maloy KJ, Salaun L, Cahill R, et al: CD4ϩCD25ϩ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 2003;197:111-119.
  710. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M: Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995;155: 1151-1164.
  711. Yu P, Lee Y, Liu W, et al: Intratumor depletion of CD4ϩ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 2005;201:779-791.
  712. Nakamura T, Sonoda KH, Faunce DE, et al: CD4ϩ NKT cells, but not conventional CD4ϩ T cells, are required to generate efferent CD8ϩ T regulatory cells following antigen inoculation in an immune-privileged site. J Immunol 2003;171:1266-1271.
  713. Nakamura T, Terajewicz A, Stein-Streilein J: Mechanisms of peripheral tolerance following intracameral inoculation are independent of IL-13 or STAT6. J Immunol 2005;175:2643-2646.
  714. Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription fac- tor Foxp3. Science 2003;299:1057-1061.
  715. Hori S, Sakaguchi S: Foxp3: a critical regulator of the development and function of regulatory T cells. Microbes Infect 2004;6:745-751.
  716. Helbig H, Gurley RC, Palestine AG, Nussenblatt RB, Caspi RR: Dual effect of ciliary body cells on T lymphocyte proliferation. Eur J Immunol 1990;20:2457-2463.
  717. Hooper P, Bora NS, Kaplan HJ, Ferguson TA: Inhibition of lymphocyte proliferation by resident ocular cells. Curr Eye Res 1991;10:363-372.
  718. Knisely TL, Bleicher PA, Vibbard CA, Granstein RD: Production of latent transforming growth factor-beta and other inhibitory factors by cultured murine iris and ciliary body cells. Curr Eye Res 1991;10:761-771.
  719. Streilein JW, Bradley D: Analysis of immunosuppressive properties of iris and ciliary body cells and their secretory products. Invest Ophthalmol Vis Sci 1991;32:2700-2710.
  720. Yoshida M, Takeuchi M, Streilein JW: Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 1. Inhibition of T-cell activation in vitro by direct cell-to-cell contact. Invest Ophthalmol Vis Sci 2000;41:811-821.
  721. Taylor AW: Ocular immunosuppressive microenvironment; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 72-89.
  722. Namba K, Kitaichi N, Nishida T, Taylor AW: Induction of regulatory T cells by the immunomodu- lating cytokines ␣-melanocyte-stimulating hormone and transforming growth factor-␤2. J Leukoc Biol 2002;72:946-952.
  723. Nishida T, Taylor AW: Specific aqueous humor factors induce activation of regulatory T cells. Invest Ophthalmol Vis Sci 1999;40:2268-2274.
  724. Taylor A, Namba K: In vitro induction of CD25ϩ CD4ϩ regulatory T cells by the neuropeptide alpha-melanocyte stimulating hormone (␣-MSH). Immunol Cell Biol 2001;79:358-367.
  725. Ferguson TA, Herndon JM, Dube P: The immune response and the eye: a role for TNF alpha in anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci 1994;35:2643-2651. Dr. Jerry Y. Niederkorn Department of Ophthalmology, University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9057 (USA)
  726. Tel. ϩ1 214 648 3829, Fax ϩ1 214 648 9061, E-Mail jerry.niederkorn@utsouthwestern.edu Niederkorn JY, Kaplan HJ (eds): Immune Response and the Eye. Chem Immunol Allergy. Basel, Karger, 2007, vol 92, pp 140-154
  727. Ferguson TA, Griffith TS: A vision of cell death: insights into immune privilege. Immunol Rev 1997;156:167-184.
  728. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189-1192.
  729. Lee HO, Herndon JM, Barreiro R, Griffith TS, Ferguson TA: TRAIL: a mechanism of tumor sur- veillance in an immune privileged site. J Immunol 2002;169:4739-4744.
  730. Streilein JW: Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 2003;74:179-185.
  731. Niederkorn JY: The immune privilege of corneal grafts. J Leukoc Biol 2003;74:167-171.
  732. Ferguson TA, Stuart PM, Herndon JM, Griffith TS: Apoptosis, tolerance, and regulatory T cells - old wine, new wineskins. Immunol Rev 2003;193:111-123.
  733. Abbas AK: Die and let live: eliminating dangerous lymphocytes. Cell 1996;84:655-657.
  734. Abbas AK, Lohr J, Knoechel B, Nagabhushanam V: T cell tolerance and autoimmunity. Autoimmun Rev 2004;3:471-475.
  735. Ferguson TA, Green DR: Fas-ligand and immune privilege: the eyes have it. Cell Death Differ 2001;8:771-772.
  736. Nagata S, Suda T: Fas and Fas ligand: lpr and gld mutations. Immunol Today 1995;16:39-43.
  737. Adachi M, Suematsu S, Suda T, et al: Enhanced and accelerated lymphoproliferation in Fas-null mice. Proc Natl Acad Sci USA 1996;93:2131-2136.
  738. Karray S, Kress C, Cuvellier S, et al: Complete loss of Fas ligand gene causes massive lympho- proliferation and early death, indicating a residual activity of gld allele. J Immunol 2004;172: 2118-2125.
  739. Stuart PM, Griffith TS, Usui N, Pepose J, Yu X, Ferguson TA: CD95 ligand (FasL)-induced apop- tosis is necessary for corneal allograft survival. J Clin Invest 1997;99:396-402.
  740. Jorgensen A, Wiencke AK, la Cour M, et al: Human retinal pigment epithelial cell-induced apop- tosis in activated T cells. Invest Ophthalmol Vis Sci 1998;39:1590-1599.
  741. Zhang J, Ma B, Marshak-Rothstein A, Fine A: Characterization of a novel cis-element that regu- lates Fas ligand expression in corneal endothelial cells. J Biol Chem 1999;274:26537-26542.
  742. Hu MS, Schwartzman JD, Yeaman GR, et al: Fas-FasL interaction involved in pathogenesis of ocu- lar toxoplasmosis in mice. Infect Immun 1999;67:928-935.
  743. Tanaka M, Suda T, Haze K, et al: Fas ligand in human serum. Nat Med 1996;2:317-322.
  744. Sotozono C, Sano Y, Suzuki T, et al: Soluble Fas ligand expression in the ocular fluids of uveitis patients. Curr Eye Res 2000;20:54-57.
  745. Hori J, Joyce N, Streilein JW: Epithelium-deficient corneal allografts display immune privilege beneath the kidney capsule. Invest Ophthalmol Vis Sci 2000;41:443-452.
  746. Ferguson TA, Herndon J, Elzey B, Griffith TS, Schoenberger S, Green DR: Uptake of apoptotic antigen-coupled cells by lymphoid dendritic cells and cross-priming of CD8 ϩ T cells produce active immune unresponsiveness. J Immunol 2002;168:5589-5595.
  747. Hill LL, Shreedhar VK, Kripke ML, Owen-Schaub LB: A critical role for Fas ligand in the active suppression of systemic immune responses by ultraviolet radiation. J Exp Med 1999;189: 1285-1294.
  748. Griffith TS, Yu X, Herndon JM, Green DR, Ferguson TA: CD95-induced apoptosis of lympho- cytes in an immune privileged site induces immunological tolerance. Immunity 1996;5:7-16.
  749. Kaplan HJ, Leibole MA, Tezel T, Ferguson TA: Fas ligand (CD95 ligand) controls angiogenesis beneath the retina. Nat Med 1999;5:292-297.
  750. Barreiro R, Schadlu R, Herndon J, Kaplan HJ, Ferguson TA: The role of Fas-FasL in the develop- ment and treatment of ischemic retinopathy. Invest Ophthalmol Vis Sci 2003;44:1282-1286.
  751. Stuart PM, Pan F, Plambeck S, Ferguson TA: FasL-Fas interactions regulate neovascularization in the cornea. Invest Ophthalmol Vis Sci 2003;44:93-98.
  752. Chen JJ, Sun Y, Nabel GJ: Regulation of the proinflammatory effects of Fas ligand (CD95L). Science 1998;282:1714-1717.
  753. Elzey BD, Griffith TS, Herndon JM, Barreiro R, Tschopp J, Ferguson TA: Regulation of Fas ligand-induced apoptosis by TNF. J Immunol 2001;167:3049-3056.
  754. Bonfoco E, Stuart PM, Brunner T, et al: Inducible nonlymphoid expression of Fas ligand is responsible for superantigen-induced peripheral deletion of T cells. Immunity 1998;9:711-720.
  755. Pinkoski MJ, Droin NM, Lin T, Genestier L, Ferguson TA, Green DR: Nonlymphoid Fas ligand in peptide-induced peripheral lymphocyte deletion. Proc Natl Acad Sci USA 2002;99:16174-16179.
  756. Hill LL, Ouhtit A, Loughlin SM, Kripke ML, Ananthaswamy HN, Owen-Schaub LB: Fas ligand: a sensor for DNA damage critical in skin cancer etiology. Science 1999;285:898-900.
  757. Gutierrez-Steil C, Wrone-Smith T, Sun X, Krueger JG, Coven T, Nickoloff BJ: Sunlight-induced basal cell carcinoma tumor cells and ultraviolet-B-irradiated psoriatic plaques express Fas ligand (CD95L). J Clin Invest 1998;101:33-39.
  758. Gregory MS, Repp AC, Holhbaum AM, Saff RR, Marshak-Rothstein A, Ksander BR: Membrane Fas ligand activates innate immunity and terminates ocular immune privilege. J Immunol 2002;169:2727-2735.
  759. Engelbert M, Gilmore MS: Fas ligand but not complement is critical for control of experimental Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 2005;46:2479-2486.
  760. Wiley SR, Schooley K, Smolak PJ, et al: Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995;3:673-682.
  761. Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A: Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 1996;271:12687-12690.
  762. Griffith TS, Chin WA, Jackson GC, Lynch DH, Kubin MZ: Intracellular regulation of TRAIL- induced apoptosis in human melanoma cells. J Immunol 1998;161:2833-2840.
  763. Griffith TS, Rauch CT, Smolak PJ, et al: Functional analysis of TRAIL receptors using mono- clonal antibodies. J Immunol 1999;162:2597-2605.
  764. Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG: The novel receptor TRAIL-R4 induces NF-B and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 1997;7:813-820.
  765. Griffith TS, Lynch DH: TRAIL: a molecule with multiple receptors and control mechanisms. Curr Opin Immunol 1998;10:559-563.
  766. Katsikis PD, Garcia-Ojeda ME, Torres-Roca JF, et al: Interleukin-1␤ converting enzyme-like pro- tease involvement in Fas-induced and activation-induced peripheral blood T cell apoptosis in HIV infection. TNF-related apoptosis-inducing ligand can mediate activation-induced T cell death in HIV infection. J Exp Med 1997;186:1365-1372.
  767. Kayagaki N, Yamaguchi N, Nakayama M, Eto H, Okumura K, Yagita H: Type I interferons (IFNs) regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on human T cells: a novel mechanism for the antitumor effects of type I IFNs. J Exp Med 1999;189:1451-1460.
  768. Zamai L, Ahmad M, Bennett IM, Azzoni L, Alnemri ES, Perussia B: Natural killer (NK) cell- mediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med 1998;88:2375-2380.
  769. Griffith TS, Wiley SR, Kubin MZ, Sedger LM, Maliszewski CR, Fanger NA: Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL. J Exp Med 1999;189:1343-1354.
  770. Fanger NA, Maliszewski CR, Schooley K, Griffith TS: Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Exp Med 1999;190:1155-1164.
  771. Kemp TJ, Elzey BD, Griffith TS: Plasmacytoid dendritic cell-derived IFN-␣ induces TNF-related apoptosis-inducing ligand/Apo-2L-mediated antitumor activity by human monocytes following CpG oligodeoxynucleotide stimulation. J Immunol 2003;171:212-218.
  772. Pan G, O'Rourke K, Chinnaiyan AM, et al: The receptor for the cytotoxic ligand TRAIL. Science 1997;276:111-113.
  773. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM: An antagonist decoy receptor and a death domain- containing receptor for TRAIL. Science 1997;277:815-818.
  774. Sheridan JP, Marsters SA, Pitti RM, et al: Control of TRAIL-induced apoptosis by a family of sig- naling and decoy receptors. Science 1997;277:818-821.
  775. Walczak H, Degli-Esposti MA, Johnson RS, et al: TRAIL-R2: a novel apoptosis-mediating recep- tor for TRAIL. EMBO J 1997;16:5386-5397.
  776. Degli-Esposti MA, Smolak PJ, Walczak H, et al: Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 1997;186:1165-1170.
  777. Marsters SA, Sheridan JP, Pitti RM, et al: A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biol 1997;7:1003-1006.
  778. Emery JG, McDonnell P, Burke MB, et al: Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998;273:14363-14367.
  779. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC: A role for CD95 ligand in pre- venting graft rejection. Nature 1995;377:630-632.
  780. Hunt JS, Vassmer D, Ferguson TA, Miller L: Fas ligand is positioned in mouse uterus and placenta to prevent trafficking of activated leukocytes between the mother and the conceptus. J Immunol 1997;158:4122-4128.
  781. Phillips TA, Ni J, Pan G, et al: TRAIL (Apo-2L) and TRAIL receptors in human placentas: impli- cations for immune privilege. J Immunol 1999;162:6053-6059.
  782. Dr. Thomas A. Ferguson Department of Ophthalmology and Visual Sciences, Washington University School of Medicine 660 South Euclid, Box 8096
  783. St. Louis, MO 63110 (USA) Tel. ϩ1 314 362 3745, Fax ϩ1 314 747 4238, E-Mail Ferguson@vision.wustl.edu References
  784. Streilein JW: Ocular immune privilege and the Faustian dilemma. The Proctor lecture. Invest Ophthalmol Vis Sci 1996;37:1940-1950.
  785. Freddo TF: Shifting the paradigm of the blood-aqueous barrier. Exp Eye Res 2001;73:581-592.
  786. Taylor AW, Streilein JW, Cousins SW: Immunoreactive vasoactive intestinal peptide contributes to the immunosuppressive activity of normal aqueous humor. J Immunol 1994;153:1080-1086.
  787. Mo JS, Streilein JW: Immune privilege persists in eyes with extreme inflammation induced by intravitreal LPS. Eur J Immunol 2001;31:3806-3815.
  788. Taylor JW: Ocular immunosuppressive microenvironment; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 72-89.
  789. Kaplan HJ, Streilein JW: Immune response to immunization via the anterior chamber of the eye. I. F1-lymphocyte-induced immune deviation. J Immunol 1977;118:809-814.
  790. Streilein JW , Niederkorn JY: Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J Exp Med 1981;153:1058-1067.
  791. Streilein JW , Niederkorn JY: Characterization of the suppressor cell(s) responsible for anterior chamber-associated immune deviation (ACAID) induced in BALB/c mice by P815 cells. J Immunol 1985;134:1381-1387.
  792. plasmin requires interaction with thrombospondin-1 and its cell surface receptor, CD36. Am J Pathol 1999;155:841-851.
  793. Mo JS, Streilein JW: Ocular trauma induced a secondary immunosuppressive microenvironment containing active TGF-beta (abstract). Invest Ophthalmol Vis Sci 2005;46:5044.
  794. D'Orazio TJ, Niederkorn JY: A novel role for TGF-beta and IL-10 in the induction of immune privilege. J Immunol 1998;160:2089-2098.
  795. Dr. Jun-Song Mo Department of Ophthalmology and Visual Sciences University of Louisville School of Medicine 301 East Muhammad Ali Boulevard, Room 3318
  796. Louisville, KY 40202 (USA) Tel. ϩ1 502 852 0733, Fax ϩ1 502 852 7311, E-Mail jun.mo@louisville.edu References
  797. Ono SJ: V ernal keratoconjunctivitis: evidence in immunoglobulin E-dependent and immunoglobu- lin E-independent eosinophilia. Clin Exp Allergy 2003;33:279-281.
  798. Stahl JL, Barney NP: Ocular allergic disease. Curr Opin Allergy Clin Immunol 2004;4:455-459.
  799. Bonini S, Bonini S: Pathogenesis of allergic conjunctivitis; in Denburg JA (ed): Allergy and Allergic Diseases: The New Mechanism and Therapeutics. Totowa, Humana Press, 1998.
  800. Bisgaard H, Ford-Hutchison AW , Charleson S, Taudorf E: Production of leukotrienes in human skin and conjunctiva after specific allergen challenge. Allergy 1985;40:417-423.
  801. Metcalfe DD, Baram D, Mekori Y A: Mast cells. Physiol Rev 1997;77:1033-1079.
  802. Leu G, Keane-Myers A, Miyazaki D, Tai A, Ono SJ: Molecular and Cellular Aspects of Allergic Conjunctivits; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 39-58.
  803. Ono SJ, Abelson MB: Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol 2005;115:118-122.
  804. Irani AMA, Butrus SI, Tabbara KF , Schwartz LB: Human conjunctival mast cell distribution of MCT and MCTC in vernal conjunctivitis and giant papillary conjunctivitis. J Allergy Clin Immunol 1990;86:34-40.
  805. Collum LMT, Kilmartin DJ: Acute allergic conjunctivitis; in Abelson MB (ed): Allergic Diseases of the Eye. Philadelphia, Saunders, 2000, pp 108-132.
  806. Proud D, Sweet J, Stein P, Settipane RA, Kagey-Sobotka A, Friedland MH, Lichtenstein LM: Inflammatory mediator release on conjunctival provocation of allergic subjects with allergen. J Allergy Clin Immunol 1990;85:896-905.
  807. Bielory L, Ghafoor S: Histamine receptors and the conjunctiva. Curr Opin Allergy Clin Immunol 2005;5:437-440.
  808. Anderson DF, Zhang S, Bradding P, McGill JI, Holgate ST, Roche WR: The relative contribution of mast cell subsets to conjunctival TH2-like cytokines. Invest Ophthalmol Vis Sci 2001;42:995-1001.
  809. Leonardi A, Borghesan F, Faggian D, Depaoli M, Secchi AG, Plebani M: Tear and serum soluble leukocyte activation markers in conjunctival allergic diseases. Am J Ophthalmol 2000;129: 151-158.
  810. Fahy GT, Easty DL, Collum LMT, et al: Double masked trial of lodoxamide and sodium cromo- glycate in allergic eye disease. A multicentered study. Eur J Ophthamol 1992;2:144-149.
  811. Leino M, Ennevaara K, Latvala AL, Nordgren P, Posti AM, Suves R, Takalo E: Double-blind group comparative study of 2% nedocromil sodium eye drops with 2% sodium cromoglycate and placebo eye drops in the treatment of seasonal allergic conjunctivitis. Clin Exp Allergy 1992;22: 929-932.
  812. Abelson MB, Smith LM: Levocabastine. Evaluation in the histamine and compound 48/80 models of ocular allergy in humans. Ophthalmology 1988;95:1494-1497.
  813. McGill JI, Holgate ST, Church MK, Anderson DF, Bacon A: Allergic eye disease mechanisms. Br J Ophthalmol 1998;82:1203-1214.
  814. Ono SJ, Nakamura T, Miyazaki D, Ohbayashi M, Dawson M, Toda M: Chemokines: role in leuko- cyte development, trafficking and effector function. J Allergy Clin Immunol 2003;111:1185-1199.
  815. Abelson MB, Madiwale N, Weston JH: Conjunctival eosinophils in allergic ocular disease. Arch Ophthalmol 1983;101:555-556.
  816. Trocme SD, Kephart G, Bourne WM, Buckley RJ, Gleich GJ: Eosinophil major basic protein deposition in human corneal shield ulcers. Invest Ophthalmol Vis Sci 1992;33(suppl):984.
  817. Foster CS, Calonge MD: Atopic keratoconjunctivitis. Ophthalmology 1990;97:992-1000.
  818. Anderson DF, Zhang S, MacLeod JDA, McGill JI, Roche WR, Holgate ST: Conjunctival mast cells are heterogenous with respect to cytokine storage. Invest Ophthalmol Vis Sci 1997;36:57-62.
  819. Bacon AS, McGill JI, Anderson DF, Baddeley S, Lightman SL, Holgate ST: Adhesion molecules and relationship to leukocyte levels in allergic eye disease. Invest Ophthalmol Vis Sci 1998;39: 322-330.
  820. Yanni JM, Weimer LK, Sharif NA, Xu SX, Gamache DA, Spellman JM: Inhibition of histamine- induced human conjunctival epithelial cell responses by ocular allergy drugs. Ann Allergy Asthma Immunol 1997;79:541-545.
  821. Bacon AS, Tuft SJ, Metz DP, McGill JI, Buckley RJ, Baddeley S, Lightman SL: The origin of ker- atopathy in chronic allergic eye disease: a histopathological study. Eye 1993;7(suppl):21-25.
  822. Morgan SJ, Williams JH, Walls AF, Church MK, Holgate ST, McGill JI: Mast cell numbers and staining characteristics in the normal and allergic human conjunctiva. J Allergy Clin Immunol 1991;87:111-116.
  823. Uchio E, Ono S, Ikezawa Z, Ohno S: Serum levels of soluble intercellular adhesion molecules-1, vascular cell adhesion molecule-1, and interleukin-2 receptor in patients with vernal kerato- conjunctivitis and allergic conjunctivitis. Allergy 1999;54:135-141.
  824. Zhang S, Anderson DF, McGill JI, Holgate ST, Roche WR: Human mast cells express stem cell factor. J Pathol 1998;186:59-66.
  825. Cook EB: Tear cytokines in acute and chronic ocular allergic inflammation. Curr Opin Allergy Clin Immunol 2004;4:441-445.
  826. Graziano FM: Conjunctival mast cells in ocular allergic disease. Allergy Asthma Proc 2001;22: 121-126.
  827. Allansmith MR, O'Connor GR: Immunoglobulin: structure, function and relation to the eye. Surv Ophthalmol 1970;14:367-402.
  828. Ryan JJ: Interleukin-4 and its receptor: essential mediator of the allergic response. J Allergy Clin Immunol 1997;99:1-5.
  829. Horan RF, Schneider LC, Sheffer AL: Allergic skin disorders and mastocytosis. JAMA 1992;268: 2858-2868.
  830. Beltrani VS: The clinical spectrum of atopic dermatitis. J Allergy Clin Immunol 1999;104: S87-S98.
  831. Tuft SJ, Kemeny DM, Dart JKG, Buckley RJ: Clinical features of atopic keratoconjunctivitis. Ophthalmology 1991;98:150-158.
  832. Lemp MA: Contact lenses and associated anterior segment disorders: dry eye, blepharitis, and allergy. Ophthalmol Clin North Am 2003;16:463-469.
  833. Robin JB, Regis-Pacheco LF, May WN, Schanzlin DJ, Smith RE: Giant papillary conjunctivitis associated with an extruded buckle. Arch Ophthalmol 1987;105:619-624.
  834. Allansmith MR, Korb DR, Grenier JV, Henriquez AS, Simon MA, Finnemore VM: Giant papillary conjunctivitis in contact lens wearers. Am J Ophthalmol 1977;83:697-708.
  835. Fowler SA, Korb DR, Finnemore VM, Allansmith MR: Surface deposits on worn hard contact lenses. Arch Ophthalmol 1984;112:757-759.
  836. Hart DE: Contact lens/tear film interactions: deposits and coatings; in Dabezies OH (ed): Contact Lenses: The CLAO Guide to Basic Science and Clinical Practice, update 7. Boston, Little Brown, 1990, vol 45, pp A-1-A-127.
  837. Boswall GJ, Ehlers WH, Liustro A, Worall M, Donshik PC: A comparison of conventional and dis- posable extended wear contact lenses. CLAO J 1993;19:158-165.
  838. Heidemann DG, Dunn SP, Siegal MJ: Unusual causes of giant papillary conjunctivitis. Cornea 1993;12:78-80.
  839. Begley CG, Riggle A, Tuel JA: Association of giant papillary conjunctivitis with seasonal aller- gies. Optom Vis Sci 1990;67:192-195.
  840. Moschos MM, Eperon S, Guex-Crosier Y: Increased eotaxin in tears of patients wearing contact lenses. Cornea 2004;23:771-775.
  841. Irkec MT, Orhan M, Erdener U: Role of tear inflammatory mediators in contact lens-associated giant papillary conjunctivitis in soft contact lens wearer. Ocul Immunol Inflamm 1999;7:35-38.
  842. Elgebaly SA, Donshik PC, Rahhal F, Williams W: Neutrophil chemotactic factors in the tears of giant papillary conjunctivitis patients. Invest Ophthalmol Vis Sci 1991;32:208-213.
  843. Sac RA, Jones B, Antignani A, Libow R, Harvey H: Specificity and biological activity of the pro- tein deposits on the hydrogel surface: relationship of polymer structure to biofilm formation. Invest Ophthalmol Vis Sci 1987;28:842-849.
  844. Ballow M, Donshik PC, Rapacz P, Maenza R, Yamase H, Muncy L: Immune responses in monkeys to lenses from patients with contact lens induced giant papillary conjunctivitis. CLAO J 1989;15: 64-70.
  845. Dinarello C: Biologic basis for inteleukin-1 in disease. Blood 1996;87:2095-2147.
  846. Robboy MW, Comstock TL, Kalsow CM: Contact lens-associated corneal infiltrates. Eye Contact Lens 2003;29:146-154.
  847. Baggiolini M, Dewald B, Moser B: Human chemokines: an update. Annu Rev Immunol 1997;15: 675-705.
  848. Moschos MM, Eperon S, Guex-Crosier Y: Increased eotaxin in tears of patients wearing contact lenses. Cornea 2004;23:771-775.
  849. Ono SJ, Nakamura T, Miyazaki D, Ohbayashi M, Dawson M, Toda M: Chemokines: role in leuko- cyte development, trafficking and effector function. J Allergy Clin Immunol 2003;111:1185-1199.
  850. Refojo MF, Holly FJ: Tear protein absorption on hydrogels: a possible cause of contact lens allergy. Contact Intraoc Lens Med J 1977;23:3-11.
  851. Nancy A, McNamara. Innate defense of the ocular surface. Eye Contact Lens 2003;29:S10-S13.
  852. Holden BA, Markides AJ: On the desirability and efficiency of chemical sterilization of hydrophilic lenses. Aust J Optom 1971;54:325-336.
  853. Baudouin C: Allergic reaction to topical eye drops. Curr Opin Allergy Clin Immunol 2005;5:459-463.
  854. Tripathi RC, Tripathi BJ, Ruben M: The pathology of soft contact lens spoilage. Ophthalmology 1980;87:369-378.
  855. Rubin M, Khoo CY: Contact Lenses, medical aspects. Pittsburgh, PG Publishing, 1989, pp 15-18. Dr. Mohammad Siddique Department of Ocular Immunology Institute of Ophthalmology and Moorfields Eye Hospital University College London, Bath Street London EC1V 9EL (UK)
  856. Tel. ϩ44 20 7608 6882, Fax ϩ44 20 7608 4044, E-Mail drmsiddique@hotmail.com References
  857. Schaumberg DA, Sullivan DA, Buring JA, Dana MR: Prevalence of dry eye syndrome among US women. Am J Ophthalmol 2003;136:318-326.
  858. Lemp MA: Report of the National Eye Institute/Industry workshop on clinical trials in dry eyes. CLAO J 1995;21:221-232.
  859. Stern ME, Beuerman R W , Fox RI, Gao J, Mircheff AK, Pflugfelder SC: The pathology of dry eye: the interaction between ocular surface and lacrimal glands. Cornea 1998;17:584-589.
  860. Dana MR, Hamrah P: Role of immunity and inflammation in corneal and ocular surface disease associated with dry eye. Adv Exp Med Biol 2002;506:729-738.
  861. Saito I, Terauchi K, Shimuta M, Nishiimura S, Yoshino K, Takeuchi T, Tsubota K, Miyasaka N: Expression of cell adhesion molecules in the salivary and lacrimal glands of Sjögren's syndrome. J Clin Lab Anal 1993;7:180-187.
  862. Gordon TP , Bolstad AI, Rischmueller M, Jonsson R, Waterman SA: Autoantibodies in primary Sjögren's syndrome: new insights into mechanisms of autoantibody diversification and disease pathogenesis. Autoimmunity 2001;34:123-132.
  863. Barabino S, Shen L, Chen L, Rashid S, Rolando M, Dana MR: The controlled environment cham- ber: a new mouse model for dry eyes. Invest Ophthalmol Vis Sci 2005;46:2766-2771.
  864. Zhu Z, Stevenson D, Schechter JE, Mircheff AK, Atkinson R, Trousdale MD: Lacrimal histo- pathology and ocular surface disease in a rabbit model of dacryoadenitis. Cornea 2003;22:25-32.
  865. Damato BE, Allan D, Murray SB, Lee WR: Senile atrophy of the human lacrimal gland: the con- tribution of chronic inflammatory disease. Br J Ophthalmol 1984;68:674-680.
  866. Mircheff AK, Gierow JP, Lee LM, Lambert RW, Akashi RH, Hofman FM: Class II antigen expres- sion by lacrimal epithelial cells. An updated working hypothesis for antigen presentation by epithelial cells. Invest Ophthalmol Vis Sci 1991;32:2302-2310.
  867. Yang T, Zeng H, Zhang J, Okamoto CT, Warren DW, Wood RL, Bachmann M, Mircheff AK: MHC class II molecules, cathepsins, and La/SSB proteins in lacrimal acinar cell endomembranes. Am J Physiol 1999;277:C994-C1007.
  868. Guo Z, Azzarolo AM, Schechter JE, Warren DW, Wood RL, Mircheff AK, Kaslow HR: Lacrimal gland epithelial cells stimulate proliferation in autologous lymphocyte preparations. Exp Eye Res 2000;71:11-22.
  869. Asano M, Toda M, Sakaguchi N, Sakaguchi S: Autoimmune disease as a consequence of develop- mental abnormality of a T cell subpopulation. J Exp Med 1996;184:387-396.
  870. Piccirillo CA, Shevach EM: Naturally-occurring CD4ϩ CD25ϩ immunoregulatory T cells: cen- tral players in the arena of peripheral tolerance. Semin Immunol 2004;16:81-88.
  871. McCartney-Francis NL, Mizel DE, Frazier-Jessen M, Kulkarni AB, McCarthy JB, Wahl SM: Lacrimal gland inflammation is responsible for ocular pathology in TGF-beta 1 null mice. Am J Pathol 1997;151:1281-1288.
  872. Mircheff AK: Sjögren's syndrome as failed local immunohomeostasis: prospects for cell-based therapy. Ocul Surf 2003;1:160-179.
  873. Rocha EM, Wickham LA, Huang Z, Toda I, Gao J, da Silveira LA, Sullivan DA: Presence and testosterone influence on the levels of anti-and pro-inflammatory cytokines in lacrimal tissues of a mouse model of Sjögren's syndrome. Adv Exp Med Biol 1998;438:485-491.
  874. Clark DA, Lamey PJ, Jarrett RF, Onions DE: A model to study viral and cytokine involvement in Sjögren's syndrome. Autoimmunity 1994;18:7-14.
  875. Ueta M, Nochi T, Jang MH, Park EJ, Igarashi O, Hino A, Kawasaki S, Shikina T, Hiroi T, Kinoshita S, Kiyono H: Intracellularly expressed TLR2s and TLR4s contribution to an immunosilent environ- ment at the ocular mucosal epithelium. J Immunol 2004;173:3337-3347.
  876. Pflugfelder SC, Jones D, Ji Z, Afonso A, Monroy D: Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca. Curr Eye Res 1999;19:201-211.
  877. Luo L, Li DQ, Doshi A, Farley W, Corrales RM, Pflugfelder SC: Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Invest Ophthalmol Vis Sci 2004;45:4293-4301.
  878. Gulati A, Sacchetti M, Bonini S, Dana MR: Chemokine receptor CCR5 expression in conjunctival epithelium of patients with dry eye syndrome. Arch Ophthalmol 2006;124:710-716.
  879. Brignole F, Pisella PJ, Goldschild M, De Saint Jean M, Goguel A, Baudouin C: Flow cytometric analysis of inflammatory markers in conjunctival epithelial cells of patients with dry eyes. Invest Ophthalmol Vis Sci 2000;41:1356-1363.
  880. Gao J, Morgan G, Tieu D, Schwalb TA, Luo JY, Wheeler LA, Stern ME: ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice. Exp Eye Res 2004;78:823-835.
  881. Stern ME, Gao J, Schwalb TA, Ngo M, Tieu DD, Chan C, Reis BL, Whitcup SM, Thompson D, Smith JA: Conjunctival T-cell subpopulations in Sjögren's and non-Sjögren's patients with dry eye. Invest Ophthalmol Vis Sci 2002;43:2609-2614.
  882. Hamrah P, Huq SO, Liu Y, Zhang Q, Dana MR: Corneal immunity is mediated by heterogeneous population of antigen-presenting cells. J Leukoc Biol 2003;74:172-178.
  883. Rashid S, Barabino S, Dana R: Changes in corneal endowment of immune cells in novel dry eye model. Invest Ophthalmol Vis Sci 2005;46:E-3585.
  884. Dr. M. Reza Dana Schepens Eye Research Institute, Department of Ophthalmology Harvard Medical School, 20 Staniford Street Boston, MA 02114 (USA) Tel. ϩ1 617 912 7404, Fax ϩ1 617 912 0117, E-Mail dana@vision.eri.harvard.edu References
  885. Khatri S, Lass JH, Heinzel FP , et al: Regulation of endotoxin-induced keratitis by PECAM-1, MIP-2, and toll-like receptor 4. Invest Ophthalmol Vis Sci 2002;43:2278-2284.
  886. Hazlett LD, Rosen DD, Berk RS: Age-related susceptibility to Pseudomonas aeruginosa ocular infection in mice. Infect Immun 1978;20:25-29.
  887. Kernacki KA, Hobden JA, Hazlett LD: Murine model of bacterial keratitis; in Zak O, Sande M (eds): Handbook of Animal Models of Infection. London, Academic Press, 1999, pp 361-366.
  888. Hazlett LD: Pathogenic mechanisms of P. aeruginosa keratitis: a review of the role of T cells, Langerhans cells, PMN, and cytokines. DNA Cell Biol 2002;21:383-390.
  889. Szliter EA, Morris CA, Carney F , et al: Development of a new extended-wear contact lens model in the rat. CLAOJ 2002;28:119-123.
  890. Szliter E, Barrett R, Gabriel M, et al: Pseudomonas aeruginosa-induced inflammation in the rat extended wear contact lens model. Eye Contact Lens 2006;32:12-18.
  891. Steuhl KP , Doring G, Henni A, et al: Relevance of host-derived and bacterial factors in Pseudomonas aeruginosa corneal infection. Invest Ophthalmol Vis Sci 1987;28:1559-1568.
  892. Hazlett LD, Rosen D, Berk RS: Experimental Pseudomonas eye infection in cyclophosphamide- treated mice. Invest Ophthalmol Vis Sci 1977;16:649-652.
  893. Hazlett LD: Corneal response to Pseudomonas aeruginosa infection. Progr Retin Eye Res 2004;23:1-30.
  894. Kernacki KA, Barrett RP, Hobden JA, et al: Macrophage inflammatory protein-2 is a mediator of polymorphonuclear neutrophil influx in ocular bacterial infection. J Immunol 2000;164:1037-1045.
  895. Niederkorn JY, Peeler JS, Mellon J: Phagocytosis of particulate antigens by corneal epithelial cells stimulates interleukin-1 secretion and migration of Langerhans cells into the central cornea. Reg Immunol 1989;2:83-90.
  896. Dinarello CA: Biological basis for interleukin-1 in disease. Blood 1996;87:2095-2147.
  897. Dinarello CA, Wolff SM: The role of interleukin-1 in disease. N Engl J Med 1993;328:106-113.
  898. Arend WP, Malyak M, Guthridge CJ, et al: Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 1998;16:27-32.
  899. Rudner XL, Kernacki KA, Barrett RP, et al: Prolonged elevation of IL-1 in Pseudomonas aerugi- nosa ocular infection regulates macrophage-inflammatory protein-2 production, polymorphonu- clear neutrophil persistence, and corneal perforation. J Immunol 2000;164:6576-6582.
  900. Kwon B, Hazlett LD: Association of CD4ϩ T cell-dependent keratitis with genetic susceptibility to Pseudomonas aeruginosa ocular infection. J Immunol 1997;159:6283-6290.
  901. Gorham JD, Güler ML, Steen RG, et al: Genetic mapping of a murine locus controlling develop- ment of T helper 1/T helper 2 type responses. Proc Natl Acad Sci 1996;93:12467-12472.
  902. Hazlett LD, McClellan S, Kwon B, et al: Increased severity of Pseudomonas aeruginosa corneal infection in strains of mice designated as Th1 versus Th2 responsive. Invest Ophthalmol Vis Sci 2000;41:805-810.
  903. Huang X, Hazlett LD: Analysis of Pseudomonas aeruginosa corneal infection using oligonu- cleotide microarray. Invest Ophthalmol Vis Sci 2003;44:3409-3416.
  904. Haelens A, Wuyts A, Proost P, et al: Leukocyte migration and activation by murine chemokines. Immunobiology 1996;195:499-521.
  905. Baggiolini M, Dewald B, Moser B: Interleukin-8 and related chemotactic chemokines -CXC and CC chemokines. Adv Immunol 1994;55:97-179.
  906. DiPietro A, Burdick M, Low AE, et al: MIP-1␣ as a critical macrophage chemoattractant in murine wound repair. J Clin Invest 1998;101:1693-1698.
  907. Shanley TP, Schmal H, Friedl HP, et al: Role of macrophage inflammatory protein-1␣ (MIP-1␣) in acute lung injury in rats. J Immunol 1995;154:4793-4802.
  908. Bonecchi R, Polentarutti N, Luini W, et al: Up-regulation of CCR1 and CCR3 and induction of chemotaxis to CC chemokines by IFN-gamma in human neutrophils. J Immunol 1999;162: 474-479.
  909. Kernacki KA, Goebel DJ, Poosch M, et al: Early cytokine and chemokine gene expression during Pseudomonas aeruginosa corneal infection in mice. Infect Immun 1998;66:376-379.
  910. Kernacki KA, Barrett RP, McClellan S, et al: MIP-1␣ regulates CD4ϩ T cell chemotaxis and indi- rectly enhances PMN persistence in Pseudomonas aeruginosa corneal infection. J Leukoc Biol 2001;70:911-919.
  911. O'Garra A: Cytokines induce the development of functionally heterogenous T helper cell subsets. Immunity 1998;8:275-283.
  912. Abbas AK, Murphy KM, Sher A: Functional diversity of helper T lymphocytes. Nature 1996;383:787-793.
  913. Locksley RM: Interleukin 12 in host defense against microbial pathogens. Proc Natl Acad Sci 1993;90:5879-5880.
  914. Bohn E, Autenrieth IB: IL-12 is essential for resistance against Yersinia enterocolitica by trigger- ing IFN-gamma production in NK cells and CD4 ϩ T cells. J Immunol 1996;156:1458-1468.
  915. Hazlett LD, Rudner XL, McClellan SA, et al: Role of IL-12 and IFN-␥ in Pseudomonas aerugi- nosa corneal infection. Invest Ophthalmol Vis Sci 2002;43:419-424.
  916. Ghayur T, Banerjee S, Hugunin M, et al: Caspase-1 processes IFN-␥-inducing factor and regulates LPS-induced IFN-␥ production. Nature 1997;386:619-623.
  917. Lu H, Shen C, Brunham RC: Chlamydia trachomatis infection of epithelial cells induces the acti- vation of caspase-1 and release of mature IL-18. J Immunol 2000;165:1463-1469.
  918. Shibuya K, Robinson D, Zonin F, et al: IL-1␣ and TNF-␣ are required for IL-12-induced develop- ment of Th1 cells producing high levels of IFN-␥ in BALB/c but not C57BL/6 mice. J Immunol 1998;160:1708-1716.
  919. Netea MG, Fantuzzi G, Kullberg BJ, et al: Neutralization of IL-18 reduces neutrophil tissue accu- mulation and protects mice against lethal Escherichia coli and Salmonella typhimurium endotox- emia. J Immunol 2000;164:2644-2649.
  920. Huang X, McClellan SA, Barrett RP, et al: IL-18 contributes to host resistance against infection with Pseudomonas aeruginosa through induction of IFN-gamma production. J Immunol 2002;68: 5756-5763.
  921. Hazlett LD, McClellan S, Goshgarian C: The role of nitric oxide in resistance to P. aeruginosa ocular infection. Ocul Immunol Inflamm 2005;13:279-288.
  922. McClellan SA, Lighvani S, Hazlett LD: IFN-gamma: regulation of nitric oxide in the P. aeruginosa- infected cornea. Ocul Immunol Inflamm 2006;14:21-28.
  923. Lighvani S, Huang X, Trivedi PP, et al: Substance P regulates NK cell IFN-␥ production and resis- tance to Pseudomonas aeruginosa infection. Eur J Immunol 2005;35:1567-1575.
  924. Hendricks RL, Janowicz M, Tumpey TM: Critical role of corneal Langerhans cells in the CD4-but not CD8-mediated immunopathology in herpes virus-1-infected mouse cornea. J Immunol 1992;148:2522-2529.
  925. Hazlett LD, Moon M, Dawisha S, et al: Age alters Langerhans cell response to P. aeruginosa ocu- lar challenge. Curr Eye Res 1986;5:343-355.
  926. Williamson JSP, Dimarco S, Streilein JW: Immunobiology of Langerhans cells on the ocular sur- face.
  927. I. Langerhans cells within the central cornea interfere with induction of anterior chamber associated immune deviation. Invest Ophthalmol Vis Sci 1987;28:1527-1532.
  928. Hazlett LD, McClellan SM, Hume EBH, et al: Extended wear contact lens usage induces Langerhans cell migration into cornea. Exp Eye Res 1999;69:575-577.
  929. Peeler JS, Niederkorn JY: Antigen presentation by Langerhans cells in vivo: donor derived Ia ϩ Langerhans cells are required for induction of delayed-type hypersensitivity but not for cytotoxic T lymphocyte responses to alloantigens. J Immunol 1986;136:4362-4371.
  930. Hazlett LD, McClellan SA, Rudner XL, et al: The role of Langerhans cells in P. aeruginosa infec- tion. Invest Ophthalmol Vis Sci 2002;43:189-197.
  931. Chaker MB, Tharp MD, Bergestresser PR: Rodent epidermal Langerhans cells demonstrate greater histochemical specificity for ADP than for ATP and AMP. J Invest Dermatol 1984;82:496-500.
  932. Hazlett LD, McClellan S, Barrett R, et al: B7/CD28 costimulation is critical in susceptibility to Pseudomonas aeruginosa corneal infection: a comparative study using monoclonal antibody blockade and CD28-deficient mice. J Immunol 2001;166:1292-1299.
  933. Barrett R, McClellan S, Huang X, et al: Cervical lymph nodes are not required for T cell traffick- ing to the cornea after Pseudomonas aeruginosa eye infection. Invest Ophthalmol Vis Sci 2003;43: ARVO E-Abstract 716.
  934. Mills CD, Kinkaid K, Alt JM, et al: M-1/M2 macrophages and Th1/Th2 paradigm. J Immunol 2000;164:6166-6173.
  935. Nathan CF: Secretory products of macrophages. J Clin Invest 1987;79:319-326.
  936. Liew FY, Li Y, Moss D, et al: Resistance to Leishmania major infection correlates with the induc- tion of nitric oxide synthase in murine macrophages. Eur J Immunol 1991;21:3009-3014.
  937. Oswald IP, Afroun S, Bray D, et al: Low response of BALB/c macrophages to priming and activat- ing signals. J Leukoc Biol 1992;52:315-322.
  938. McClellan SA, Huang X, Barrett RP, et al: Macrophages restrict Pseudomonas aeruginosa growth, regulate polymorphonuclear neutrophil influx and balance pro-and anti-inflammatory cytokines in BALB/c mice. J Immunol 2003;170:5219-5227.
  939. Johnson AC, Heinzel FP, Diaconu E, et al: Activation of Toll-like receptor (TLR)2, TLR4, and TLR9 in the mammalian cornea induces MyD88-dependent corneal inflammation. Invest Ophthalmol Vis Sci 2005;46:589-595.
  940. Zhang J, Xu K, Ambati B, et al: Toll-like receptor 5-mediated corneal epithelial inflammatory responses to Pseudomonas aeruginosa flagellin. Invest Ophthalmol Vis Sci 2003;44:4247-4254. Dr. Linda D. Hazlett Department of Anatomy and Cell Biology Wayne State University School of Medicine 540 East Canfield Avenue Detroit, MI 48201 (USA) Tel. ϩ1 313 577 1079, Fax ϩ1 313 577 3125, E-Mail lhazlett@med.wayne.edu References
  941. Foster CS, Streilein JW: Basic immunology; in Foster CS, Azar DT, Dohlman CH (eds): The Cornea. Scientific Foundations and Clinical Practice, ed 4. Philadelphia, Lippincott Williams & Wilkins, 2005, pp 59-102.
  942. Hamrah P, Huq SO, Liu Y, Zhang Q, Dana MR: Corneal immunity is mediated by heterogeneous population of antigen-presenting cells. J Leukoc Biol 2003;74:172-178.
  943. Foster CS: Mooren' s ulcer; in Foster CS, Azar DT, Dohlman CH (eds): The Cornea. Scientific Foundations and Clinical Practice, ed 4. Philadelphia, Lippincott Williams & Wilkins, 2005, pp 551-557.
  944. Gottsch JD, Liu SH: Cloning and expression of human corneal calgranulin C (CO-Ag). Curr Eye Res 1998;17:870-874.
  945. Gottsch JD, Li Q, Ashraf F , O'Brien TP , Stark WJ, Liu SH: Cytokine-induced calgranulin C expression in keratocytes. Clin Immunol 1999;91:34-40.
  946. Taylor CJ, Smith SI, Morgan CH, et al: HLA and Mooren' s ulceration. Br J Ophthalmol 2000;84:72-75.
  947. Xie H, Chen J, Zheng H, Li Y , Liu W: A histochemical and immunohistochemical study of cornea and adjacent bulbar conjunctiva in Mooren's ulcer (in Chinese). Yan Ke Xue Bao 2000;16:139-142.
  948. Ye J, Chen J, Kim JC, Yao K: Bone marrow-derived cells are present in Mooren's ulcer. Ophthalmic Res 2004;36:151-155.
  949. Wang Z, Chen J, Zheng H: Changes in local immune functions in Mooren' s ulcer. Y an Ke Xue Bao 1996;12:33-35.
  950. Murray PI, Rahi AH: Pathogenesis of Mooren's ulcer. Br J Ophthalmol 1984;68:182-187.
  951. Martin NF, Stark WJ, Maumenee AE: Treatment of Mooren's and Mooren's-like ulcer by lamellar keratectomy: report of six eyes and literature review. Ophthalmic Surg 1987;18:564-569.
  952. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189-1192.
  953. Weyand CM, Goronzy JJ: The molecular basis of rheumatoid arthritis. J Mol Med 1997;75: 772-785.
  954. Stastny P: Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 1978;298:869-871.
  955. Friedlaender MH: Ocular allergy and immunology. J Allergy Clin Immunol 1979;63:51-60.
  956. Riley GP, Harrall RL, Watson PG, Cawston TF, Hazleman BL: Collagenase (MMP-1) and TIMP-1 in destructive corneal disease associated with rheumatoid arthritis. Eye 1995;9:703-718.
  957. Prada J, Noelle B, Baatz H, Hartmann C, Pleyer U: Tumor necrosis factor alpha and interleukin 6 gene expression in keratocytes from patients with rheumatoid corneal ulceration. Br J Ophthalmol 2003;87:548-550.
  958. Smith VA, Rishmawi H, Hussein H, Easty DL: Tear film MMP accumulation and corneal disease. Br J Ophthalmol 2001;85:147-153.
  959. Smith VA, Hoh HB, Easty DL: Role of ocular matrix metalloproteinases in peripheral ulcerative keratitis. Br J Ophthalmol 1999;83:1376-1383.
  960. Reynolds I, John SL, Tullo AB, et al: Characterization of two corneal epithelium-derived antigens associated with vasculitis. Invest Ophthalmol Vis Sci 1998;39:2594-2601.
  961. Kumari S, Bhol KC, Simmons RK, et al: Identification of ocular cicatricial pemphigoid antibody binding site(s) in human ␤4 integrin. Invest Ophthalmol Vis Sci 2001;42:379-385.
  962. Hsu RC, Lazarova Z, Lee HG, Tung YC, Yu HS: Antiepiligrin cicatricial pemphigoid. J Am Acad Dermatol 2000;42:841-844.
  963. Akpek EK, Ilhan-Sarac O: Cicatrizing conjunctivitis; in Foster CS, Azar DT, Dohlman CH (eds): The Cornea. Scientific Foundations and Clinical Practice, ed 4. Philadelphia, Lippincott Williams & Wilkins, 2005, pp 477-502.
  964. Sacks EH, Jakobiec FA, Wieczorek R, Donnenfeld E, Perry H, Knowles DM Jr: Immuno- phenotypic analysis of the inflammatory infiltrate in ocular cicatricial pemphigoid. Further evi- dence for a T cell-mediated disease. Ophthalmology 1989;96:236-243.
  965. Roat MI, Sossi G, Lo CY, Thoft RA: Hyperproliferation of conjunctival fibroblasts from patients with cicatricial pemphigoid. Arch Ophthalmol 1989;107:1064-1067. Dr. M. Reza Dana Schepens Eye Research Institute Harvard Medical School, 20 Staniford Street Boston, MA 02114 (USA) Tel. ϩ1 617 912 7404, Fax ϩ1 617 912 0117, E-Mail dana@vision.eri.harvard.edu
  966. Niederkorn JY, Kaplan HJ (eds): Immune Response and the Eye. Chem Immunol Allergy. Basel, Karger, 2007, vol 92, pp 203-212 References
  967. Metcalf JF , Hamilton DS, Reichert R W: Herpetic keratitis in athymic (nude) mice. Infect Immun 1979;26:1164-1171.
  968. Newell CK, Martin S, Sendele D, Mercadal CM, Rouse BT: Herpes simplex virus-induced stro- mal keratitis: role of T-lymphocyte subsets in immunopathology. J Virol 1989;63:769-775.
  969. Hendricks RL, Tumpey TM: Contribution of virus and immune factors to herpes simplex virus type 1-induced corneal pathology. Invest Ophthalmol Vis Sci 1990;31:1929-1939.
  970. Brissette-Storkus CS, Reynolds SA, Lepisto AJ, Hendricks RL: Identification of a novel macrophage population in the normal mouse corneal stroma. Invest Ophthalmol Vis Sci 2002;43:2264-2271.
  971. Hamrah P, Liu Y, Zhang Q, Dana MR: The corneal stroma is endowed with a significant number of resident dendritic cells. Invest Ophthalmol Vis Sci 2003;44:581-589.
  972. Hamrah P , Zhang Q, Liu Y , Dana MR: Novel characterization of MHC class II-negative population of resident corneal Langerhans cell-type dendritic cells. Invest Ophthalmol Vis Sci 2002;43:639-646.
  973. Hendricks RL, Janowicz M, Tumpey TM: Critical role of corneal Langerhans cells in the CD4-but not CD8-mediated immunopathology in herpes simplex virus-1-infected mouse corneas. J Immunol 1992;148:2522-2529.
  974. Tang Q, Chen W , Hendricks RL: Proinflammatory functions of IL-2 in herpes simplex virus corneal infection. J Immunol 1997;158:1275-1283.
  975. Tang Q, Hendricks RL: Interferon gamma regulates platelet endothelial cell adhesion molecule 1 expression and neutrophil infiltration into herpes simplex virus-infected mouse corneas. J Exp Med 1996;184:1435-1447.
  976. Babu JS, Kanangat S, Rouse BT: T cell cytokine mRNA expression during the course of the immunopathologic ocular disease herpetic stromal keratitis. J Immunol 1995;154:4822-4829.
  977. Keadle TL, Stuart PM: Interleukin-10 (IL-10) ameliorates corneal disease in a mouse model of recurrent herpetic keratitis. Microb Pathog 2005;38:13-21.
  978. Tumpey TM, Elner VM, Chen SH, Oakes JE, Lausch RN: Interleukin-10 treatment can suppress stromal keratitis induced by herpes simplex virus type 1. J Immunol 1994;153:2258-2265.
  979. Keadle TL, Usui N, Laycock KA, Miller JK, Pepose JS, Stuart PM: IL-1 and TNF-alpha are important factors in the pathogenesis of murine recurrent herpetic stromal keratitis. Invest Ophthalmol Vis Sci 2000;41:96-102.
  980. Maertzdorf J, Osterhaus AD, Verjans GM: IL-17 expression in human herpetic stromal keratitis: modulatory effects on chemokine production by corneal fibroblasts. J Immunol 2002;169: 5897-5903.
  981. Zheng M, Deshpande S, Lee S, Ferrara N, Rouse BT: Contribution of vascular endothelial growth factor in the neovascularization process during the pathogenesis of herpetic stromal keratitis. J Virol 2001;75:9828-9835.
  982. Biswas PS, Rouse BT: Early events in HSV keratitis -setting the stage for a blinding disease. Microbes Infect 2005;7:799-810.
  983. Deshpande S, Zheng M, Lee S, Banerjee K, Gangappa S, Kumaraguru U, Rouse BT: Bystander activation involving T lymphocytes in herpetic stromal keratitis. J Immunol 2001;167:2902-2910.
  984. Gangappa S, Deshpande SP, Rouse BT: Bystander activation of CD4ϩ T cells accounts for her- petic ocular lesions. Invest Ophthalmol Vis Sci 2000;41:453-459.
  985. Gangappa S, Deshpande SP, Rouse BT: Bystander activation of CD4ϩ T cells can represent an exclusive means of immunopathology in a virus infection. Eur J Immunol 1999;29:3674-3682.
  986. Panoutsakopoulou V, Sanchirico ME, Huster KM, Jansson M, Granucci F, Shim DJ, Wucherpfennig KW, Cantor H: Analysis of the relationship between viral infection and auto- immune disease. Immunity 2001;15:137-147.
  987. Huster KM, Panoutsakopoulou V, Prince K, Sanchirico ME, Cantor H: T cell-dependent and -independent pathways to tissue destruction following herpes simplex virus-1 infection. Eur J Immunol 2002;32:1414-1419.
  988. Zhao ZS, Granucci F, Yeh L, Schaffer PA, Cantor H: Molecular mimicry by herpes simplex virus- type 1: autoimmune disease after viral infection. Science 1998;279:1344-1347.
  989. Avery AC, Zhao ZS, Rodriguez A, Bikoff EK, Soheilian M, Foster CS, Cantor H: Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide. Nature 1995;376:431-433.
  990. Gangappa S, Babu JS, Thomas J, Daheshia M, Rouse BT: Virus-induced immunoinflammatory lesions in the absence of viral antigen recognition. J Immunol 1998;161:4289-4300.
  991. Deshpande SP, Lee S, Zheng M, Song B, Knipe D, Kapp JA, Rouse BT: Herpes simplex virus- induced keratitis: evaluation of the role of molecular mimicry in lesion pathogenesis. J Virol 2001;75:3077-3088.
  992. Verjans GM, Remeijer L, Mooy CM, Osterhaus AD: Herpes simplex virus-specific T cells infil- trate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells. Invest Ophthalmol Vis Sci 2000;41:2607-2612.
  993. Whittum JA, Niederkorn JY, McCulley JP, Streilein JW: Intracameral inoculation of herpes sim- plex virus type I induces anterior chamber associated immune deviation. Curr Eye Res 1983;2:691-697.
  994. Streilein JW: Immune regulation and the eye: a dangerous compromise. FASEB J 1987;1:199-208.
  995. Ksander BR, Hendricks RL: Cell-mediated immune tolerance to HSV-1 antigens associated with reduced susceptibility to HSV-1 corneal lesions. Invest Ophthalmol Vis Sci 1987;28:1986-1993.
  996. Tumpey TM, Fenton R, Molesworth-Kenyon S, Oakes JE, Lausch RN: Role for macrophage inflammatory protein 2 (MIP-2), MIP-1␣, and interleukin-1␣ in the delayed-type hypersensitivity response to viral antigen. J Virol 2002;76:8050-8057.
  997. Yan XT, Tumpey TM, Kunkel SL, Oakes JE, Lausch RN: Role of MIP-2 in neutrophil migration and tissue injury in the herpes simplex virus-1-infected cornea. Invest Ophthalmol Vis Sci 1998;39:1854-1862.
  998. Chen H, Hendricks RL: B7 costimulatory requirements of T cells at an inflammatory site. J Immunol 1998;160:5045-5052.
  999. Seo SK, Park HY, Choi JH, Kim WY, Kim YH, Jung HW, Kwon B, Lee HW, Kwon BS: Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis. J Immunol 2003;171:576-583. Dr. Robert L. Hendricks Eye and Ear Institute, University of Pittsburgh Room 922, 203 Lothrop Street Pittsburgh, PA 15213 (USA) Tel. ϩ1 412 647 5754, Fax ϩ1 412 647 5880, E-Mail hendricksrr@msx.upmc.edu References
  1000. Wacker WB, Donoso LA, Kalsow CM, Y ankeelov JA Jr, Organisciack DT: Experimental allergic uveitis. Isolation, characterization and localization of a soluble uveitopathogenic antigen from the bovine retina. J Immunol 1977;119:1949-1958.
  1001. Wacker WB: Experimental allergic uveitis. Investigations of retinal autoimmunity and the immunopathologic responses evoked. Invest Ophthalmol Vis Sci 1991;32:3119-3129.
  1002. Bora NS, Sohn JH, Kang SG, Cruz JM, Nishihori H, Suk HJ, Wang Y , Kaplan HJ, Bora PS: T ype I collagen is the autoantigen in experimental autoimmune anterior uveitis. J Immunol 2004;172: 7086-7094.
  1003. Nussenblatt RB: The natural history of uveitis. Int Ophthalmol 1990;14:303-308.
  1004. Darrell R W , Wagener HP , Kurland LT: Epidemiology of uveitis: incidence and prevalence in a small urban community. Arch Ophthalmol 1962;68:502-514.
  1005. Gritz DC, Wong IG: Incidence and prevalence of uveitis in Northern California: the Northern California Epidemiology of Uveitis Study. Ophthalmology 2004;111:491-500.
  1006. Knox EG, Mayho A, Cant W, Truelove P: Iridocyclitis: incidence, distribution and health service usage. Community Med 1980;2:97-101.
  1007. Bloch-Michel E, Nussenblatt RB: International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 1987;103:234-235.
  1008. 9 Chang JH, McCluskey PJ, Wakefield D: Acute anterior uveitis and HLA-B27. Surv Ophthalmol 2005;50:364-388.
  1009. Takeda K, Akira S: Toll-like receptors in innate immunity. Int Immunol 2005;17:1-14.
  1010. Poltorak A, He X, Smirnova I, Liu MY, van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998;282: 2085-2088.
  1011. Li Q, Peng B, Whitcup SM, Jang SU, Chan CC: Endotoxin induced uveitis in the mouse: suscepti- bility and genetic control. Exp Eye Res 1995;61:629-632.
  1012. de Groot-Mijnes JDF, de Visser L, Rothova A, Schuller M, van Loon AM, Weersink AJL: Rubella virus is associated with Fuchs heterochromic iridocyclitis. Am J Ophthalmol 2006;141:212-214.
  1013. Nussenblatt RB, Whitcup SM, Palestine AG: Uveitis: Fundamentals and Clinical Practice. St. Louis, Mosby, 1996, p 413.
  1014. Wakefield D, Dunlop I, McClusky PJ, Penny R: Uveitis: aetiology and disease associations in an Australian population. Aust NZ J Ophthalmol 1986;14:181-187.
  1015. Caspi RR: Basic mechanisms in immune-mediated uveitic disease; in Lightman SL (ed): Immunology of Eye Disease. Lancaster, Kluwer, 1989, pp 61-86.
  1016. Caspi RR: Immunogenetic aspects of clinical and experimental uveitis. Reg Immunol 1992;4: 321-330.
  1017. Gery I, Wiggert B, Redmond RM, Kuwabara T, Crawford MA, Vistica BP, Chader GJ: Uveoretinitis and pinealitis induced by immunization with interphotoreceptor retinoid-binding protein. Invest Ophthalmol Vis Sci 1986;27:1296-1300.
  1018. Schalken JJ, Winkens HJ, Van Vugt AH, Bovee-Geurts PHM, deGrip WJ, Broekhuyse RM: Rhodopsin-induced experimental autoimmune uveoretinitis: dose-dependent clinicopathological features. Exp Eye Res 1988;47:135-145.
  1019. Donoso LA, Dua HS, Forrester JV, Lee RH: Immunogenicity of a retinal photoreceptor cell pro- tein, phosducin. Invest Ophthalmol Vis Sci 1993;34:1476.
  1020. Ichikawa T, Taguchi O, Takahashi T, Ikeda H, Takeuchi M, Tanaka T, Usui M, Nishizuka Y: Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus. Clin Exp Immunol 1991;86:112-117.
  1021. Rosenbaum JT, McDevitt HO, Guss RB, Egbert PR: Endotoxin-induced uveitis in rats as a model for human disease. Nature 1980;286:611-613.
  1022. Bhattacherjee P, Williams RN, Eakins KE: An evaluation of ocular inflammation following the injection of bacterial endotoxin into the rat foot pad. Invest Ophthalmol Vis Sci 1983;24:196-202.
  1023. Okumura A, Mochizuki M: Endotoxin-induced uveitis in rats: morphological and biochemical study. Jpn J Ophthalmol 1988;32:457-465.
  1024. Herbort CP, Chan CC, Nussenblatt RB: Endotoxin-induced uveitis in the rat: a hypothesis for pref- erential involvement of the anterior uvea. Curr Eye Res 1990;9:119-124.
  1025. Fujino Y, Hum QL, Hikita N, Nussenblatt RB, Gery I, Chan CC: Immunopathology of experimen- tal autoimmune uveoretinitis in primates. Autoimmunity 1992;13:303-309.
  1026. Rao NA, Wacker WB, Marak GE Jr: Experimental allergic uveitis: clinicopathologic features associated with varying doses of S antigen. Arch Ophthalmol 1979;97:1954-1958.
  1027. Broekhuyse RM, Kuhlmann ED, Winkens HJ, Van Vugt AH: Experimental autoimmune anterior uveitis (EAAU), a new form of experimental uveitis. I. Induction by a detergent-insoluble, intrin- sic protein fraction of the retina pigment epithelium. Exp Eye Res 1991;52:465-474.
  1028. Broekhuyse RM, Kuhlmann ED, Winkens HJ: Experimental autoimmune anterior uveitis (EAAU). II. Dose-dependent induction and adoptive transfer using a melanin-bound antigen of the retina pigment epithelium. Exp Eye Res 1992;55:401-411.
  1029. Broekhuyse RM, Kuhlmann ED, Winkens HJ: Experimental autoimmune anterior uveitis (EAAU). III. Induction by immunization with purified uveal and skin melanins. Exp Eye Res 1993;56:575-583.
  1030. Broekhuyse RM, Kuhlmann ED: Experimental autoimmune anterior uveitis. The preparation of uveitogenic ocular melanin. Invest Ophthalmol Vis Sci 1993;34:698-700.
  1031. Chan CC, Hikita N, Dastgheib K, Whitcup SM, Gery I, Nussenblatt RB: Experimental melanin- protein-induced uveitis in the Lewis rat: immunopathologic processes. Ophthalmology 1994;101: 1275-1280.
  1032. Bora NS, Kim MC, Kabeer NH, Simpson SC, Tandhasetti MT, Cirrito TP, Kaplan AD, Kaplan HJ: Experimental autoimmune anterior uveitis: induction with melanin-associated antigen from the iris and ciliary body. Invest Ophthalmol Vis Sci 1995;36:1056-1066.
  1033. Kim MC, Kabeer NH, Tandhasetti MT, Kaplan HJ, Bora NS: Immunohistochemical studies on melanin associated antigen (MAA) induced experimental autoimmune anterior uveitis (EAAU). Curr Eye Res 1995;14:703-710.
  1034. Broekhuyse RM, Winkens HJ, Kuhlmann ED: Intraperitoneally injected melanin is highly uveito- genic. Exp Eye Res 1996;62:199-200.
  1035. Simpson SC, Kaplan HJ, Bora NS: Uveitogenic proteins isolated from bovine iris and ciliary body. Eye 1997;11:206-208.
  1036. Bora NS, Woon MD, Tandhasetti MT, Cirrito TP, Kaplan HJ: Induction of experimental autoim- mune anterior uveitis (EAAU) by a self-antigen: melanin complex without adjuvant. Invest Ophthalmol Vis Sci 1997;38:2171-2175.
  1037. Woon MD, Kaplan HJ, Bora NS: Kinetics of cytokine production in experimental autoimmune anterior uveitis (EAAU). Curr Eye Res 1998;17:955-961.
  1038. Whitcup SM, Kozhich AT, Lobanoff M, Wolitzky BM, Chan CC: Blocking both E-selectin and P-selectin inhibits endotoxin-induced leukocyte infiltration into the eye. Clin Immunol Immunopathol 1997;83:45-52.
  1039. Brito BE, Zamora DO, Bonnah RA, Pan Y, Planck SR, Rosenbaum JT: Toll-like receptor 4 and CD14 expression in human ciliary body and TLR-4 in human iris endothelial cells. Exp Eye Res 2004;79:203-208.
  1040. Woods AC: Uveitis associated with collagen disease; in Endogenous Inflammation of the Uveal Tract. Baltimore, Williams & Wilkins, 1992, p 275.
  1041. Streilein JW: Immunologic privilege of the eye. Springer Semin Immunopathol 1999;21:95-111.
  1042. Streilein JW, Niederkorn JY: Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J Exp Med 1981;153:1058-1067.
  1043. Kaplan HJ, Streilein JW: Immune response to immunization via the anterior chamber of the eye. I. F1-lymphocyte-induced immune deviation. J Immunol 1977;118:809-814.
  1044. Kaplan HJ, Streilein JW: Immune response to immunization via the anterior chamber of the eye. II. An analysis of F1 lymphocyte-induced immune deviation. J Immunol 1978;120:689-693.
  1045. Roberge FG, De Kozak Y, Utsumi T, Faure JP, Nussenblatt RB: Immune response to intraocular injection of retinal S-antigen in adjuvant. Graefes Arch Clin Exp Ophthalmol 1989;227:67-71.
  1046. Hara Y, Capsi RR, Wiggert B, Chan CC, Streilein JW: Use of ACAID to suppress interphotore- ceptor retinoid binding protein-induced experimental autoimmune uveitis. Curr Eye Res 1992; 11(suppl):97-100.
  1047. Thurau SR, Chan CC, Suh E, Nussenblatt RB: Induction of oral tolerance to S-antigen induced experimental autoimmune uveitis by a uveitogenic 20mer peptide. J Autoimmun 1991;4:507-516.
  1048. Nussenblatt RB, Caspi RR, Mahdi R, Chan CC, Roberge F, Lider O, Weiner HL: Inhibition of S-antigen induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-antigen. J Immunol 1990;144:1689-1695.
  1049. Sasamoto Y, Kawano YI, Bouligny R, Wiggert B, Chader GJ, Gery I: Immunomodulation of experimental autoimmune uveoretinitis by intravenous injection of uveitogenic peptides. Invest Ophthalmol Vis Sci 1992;33:2641-2649.
  1050. Dua HS, Abrams MS, Barrett JA, Donoso LA: The effect of retinal autoantigens and their peptides on the inhibition of experimental autoimmune uveitis. Eye 1992;6:447-452. Dr. Nalini S. Bora Department of Ophthalmology, Pat and Willard Walker Eye Research Center Jones Eye Institute, University of Arkansas for Medical Sciences 4301 West Markham, 523
  1051. Little Rock, AR 72205-7199 (USA) Tel. ϩ1 501 686 8293, Fax ϩ1 501 686 8316, E-Mail NBora@UAMS.edu References
  1052. Wax MB, Tezel G: Neurobiology of glaucomatous optic neuropathy: diverse cellular events in neurodegeneration and neuroprotection. Mol Neurobiol 2002;26:45-55.
  1053. Tezel G, Wax MB: The immune system and glaucoma. Curr Opin Ophthalmol 2004;15:80-84.
  1054. Tezel G, Wax MB: Glial modulation of retinal ganglion cell death in glaucoma. J Glaucoma 2003;12:63-68.
  1055. Gregerson DS: Immune privilege in the retina. Ocul Immunol Inflamm 1998;6:257-267.
  1056. Streilein JW, Okamoto S, Sano Y, Taylor AW: Neural control of ocular immune privilege. Ann NY Acad Sci 2000;917:297-306.
  1057. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189-1192.
  1058. Raivich G, Jones LL, Kloss CU, Werner A, Neumann H, Kreutzberg GW: Immune surveillance in the injured nervous system: T-lymphocytes invade the axotomized mouse facial motor nucleus and aggregate around sites of neuronal degeneration. J Neurosci 1998;18:5804-5816.
  1059. Hickey WF, Hsu BL, Kimura H: T-lymphocyte entry into the central nervous system. J Neurosci Res 1991;28:254-260.
  1060. Schwartz M, Kipnis J: Protective autoimmunity: regulation and prospects for vaccination after brain and spinal cord injuries. Trends Mol Med 2001;7:252-258.
  1061. Kipnis J, Mizrahi T, Hauben E, Shaked I, Shevach E, Schwartz M: Neuroprotective autoimmunity: naturally occurring CD4ϩCD25ϩ regulatory T cells suppress the ability to withstand injury to the central nervous system. Proc Natl Acad Sci USA 2002;99:15620-15625.
  1062. Schwartz M, Kipnis J: Autoimmunity on alert: naturally occurring regulatory CD4 ϩ CD25 ϩ T cells as part of the evolutionary compromise between a 'need' and a 'risk'. Trends Immunol 2002;23: 530-534. Schwartz M: Neuroprotection as a treatment for glaucoma: pharmacological and immunological approaches. Eur J Ophthalmol 2003;13(suppl 3):S27-S31.
  1063. Schwartz M: Neurodegeneration and neuroprotection in glaucoma: development of a therapeutic neuroprotective vaccine: the Friedenwald lecture. Invest Ophthalmol Vis Sci 2003;44:1407-1411.
  1064. Yang J, Patil RV, Yu H, Gordon M, Wax MB: T cell subsets and sIL-2R/IL-2 levels in patients with glaucoma. Am J Ophthalmol 2001;131:421-426.
  1065. Wax MB, Barrett DA, Pestronk A: Increased incidence of paraproteinemia and autoantibodies in patients with normal-pressure glaucoma. Am J Ophthalmol 1994;117:561-568.
  1066. Tezel G, Edward DP, Wax MB: Serum autoantibodies to optic nerve head glycosaminoglycans in patients with glaucoma. Arch Ophthalmol 1999;117:917-924.
  1067. Romano C, Barrett DA, Li Z, Pestronk A, Wax MB: Anti-rhodopsin antibodies in sera from patients with normal-pressure glaucoma. Invest Ophthalmol Vis Sci 1995;36:1968-1975.
  1068. Wax MB, Tezel G, Saito I, Gupta RS, Harley JB, Li Z, Romano C: Anti-Ro/SS-A positivity and heat shock protein antibodies in patients with normal-pressure glaucoma (see comments). Am J Ophthalmol 1998;125:145-157.
  1069. Tezel G, Seigel GM, Wax MB: Autoantibodies to small heat shock proteins in glaucoma. Invest Ophthalmol Vis Sci 1998;39:2277-2287.
  1070. Yang J, Tezel G, Patil RV, Romano C, Wax MB: Serum autoantibody against glutathione S-transferase in patients with glaucoma. Invest Ophthalmol Vis Sci 2001;42:1273-1276.
  1071. Wax MB, Tezel G, Edward PD: Clinical and ocular histopathological findings in a patient with normal-pressure glaucoma (see comments). Arch Ophthalmol 1998;116:993-1001.
  1072. Tezel G, Kass MA, Kolker AE, Wax MB: Comparative optic disc analysis in normal pressure glaucoma, primary open-angle glaucoma, and ocular hypertension. Ophthalmology 1996;103: 2105-2113.
  1073. Tezel G, Wax MB: Inhibition of caspase activity in retinal cell apoptosis induced by various stim- uli in vitro. Invest Ophthalmol Vis Sci 1999;40:2660-2667.
  1074. Tezel G, Wax MB: The mechanisms of hsp27 antibody-mediated apoptosis in retinal neuronal cells. J Neurosci 2000;20:3552-3562.
  1075. Wax MB, Tezel G, Kawase K, Kitazawa Y: Serum autoantibodies to heat shock proteins in glau- coma patients from Japan and the United States. Ophthalmology 2001;108:296-302.
  1076. Romano C, Li Z, Arendt A, Hargrave PA, Wax MB: Epitope mapping of anti-rhodopsin antibodies from patients with normal pressure glaucoma. Invest Ophthalmol Vis Sci 1999;40:1275-1280.
  1077. Maruyama I, Ohguro H, Ikeda Y: Retinal ganglion cells recognized by serum autoantibody against gamma-enolase found in glaucoma patients. Invest Ophthalmol Vis Sci 2000;41:1657-1665.
  1078. Kremmer S, Kreuzfelder E, Klein R, Bontke N, Henneberg-Quester KB, Steuhl KP, Grosse-Wilde H: Antiphosphatidylserine antibodies are elevated in normal tension glaucoma. Clin Exp Immunol 2001;125:211-215.
  1079. Joachim SC, Pfeiffer N, Grus FH: Autoantibodies in patients with glaucoma: a comparison of IgG serum antibodies against retinal, optic nerve, and optic nerve head antigens. Graefes Arch Clin Exp Ophthalmol 2005;243:817-823.
  1080. Tezel G, Wax MB: Hypoxia-inducible factor 1␣ in the glaucomatous retina and optic nerve head. Arch Ophthalmol 2004;122:1348-1356.
  1081. Tezel G, Yang X, Cai J: Proteomic identification of oxidatively modified retinal proteins in a chronic pressure-induced rat model of glaucoma. Invest Ophthalmol Vis Sci 2005;46:3177-3187.
  1082. Tezel G, Hernandez MR, Wax MB: Immunostaining of heat shock proteins in the retina and optic nerve head of normal and glaucomatous eyes. Arch Ophthalmol 2000;118:511-518.
  1083. Tezel GM, Seigel GM, Wax MB: Density-dependent resistance to apoptosis in retinal cells. Curr Eye Res 1999;19:377-388.
  1084. Young DB: Heat-shock proteins: immunity and autoimmunity. Curr Opin Immunol 1992;4: 396-400.
  1085. van Noort JM: Multiple sclerosis: an altered immune response or an altered stress response? J Mol Med 1996;74:285-296.
  1086. Young RA, Elliott TJ: Stress proteins, infection, and immune surveillance. Cell 1989;59:5-8.
  1087. van Eden W: Heat-shock proteins as immunogenic bacterial antigens with the potential to induce and regulate autoimmune arthritis. Immunol Rev 1991;121:5-28.
  1088. Maehlen J, Olsson T, Zachau A, Klareskog L, Kristensson K: Local enhancement of major histo- compatibility complex (MHC) class I and II expression and cell infiltration in experimental aller- gic encephalomyelitis around axotomized motor neurons. J Neuroimmunol 1989;23:125-132.
  1089. Molleston MC, Thomas ML, Hickey WF: Novel major histocompatibility complex expression by microglia and site-specific experimental allergic encephalomyelitis lesions in the rat central ner- vous system after optic nerve transection. Adv Neurol 1993;59:337-348.
  1090. Tezel G, Chauhan BC, LeBlanc RP, Wax MB: Immunohistochemical assessment of the glial mitogen-activated protein kinase activation in glaucoma. Invest Ophthalmol Vis Sci 2003;44: 3025-3033.
  1091. Yang J, Yang P, Tezel G, Patil RV, Hernandez MR, Wax MB: Induction of HLA-DR expression in human lamina cribrosa astrocytes by cytokines and simulated ischemia. Invest Ophthalmol Vis Sci 2001;42:365-371.
  1092. Neufeld AH: Microglia in the optic nerve head and the region of parapapillary chorioretinal atro- phy in glaucoma. Arch Ophthalmol 1999;117:1050-1056.
  1093. Tezel G, Wax MB: Increased production of tumor necrosis factor-alpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal gan- glion cells. J Neurosci 2000;20:8693-8700.
  1094. Mitrovic B, Martin FC, Charles AC, Ignarro LJ, Anton PA, Shanahan F, Merrill JE: Neurotransmitters and cytokines in CNS pathology. Prog Brain Res 1994;103:319-330.
  1095. Streit WJ: The role of microglia in brain injury. Neurotoxicology 1996;17:671-678.
  1096. Stoll G, Jander S: The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 1999;58:233-247.
  1097. Aloisi F: The role of microglia and astrocytes in CNS immune surveillance and immunopathology. Adv Exp Med Biol 1999;468:123-133.
  1098. Carson MJ: Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis. Glia 2002;40:218-231.
  1099. Dr. Gülgün Tezel Kentucky Lions Eye Center, University of Louisville School of Medicine 301 East Muhammad Ali Boulevard Louisville, KY 40202 (USA)
  1100. Tel. ϩ1 502 852 7395, Fax ϩ1 502 852 3811, E-Mail gulgun.tezel@louisville.edu References
  1101. Forrester JV, Liversidge J, Dua HS, Towler H, McMenamin PG: Comparison of clinical and exper- imental uveitis. Curr Eye Res 1990;9(suppl):75-84.
  1102. Forrester JV, Okada A, BenEzra D, Ohno S: Posterior Segment Intraocular Inflammation: Guidelines. The Hague, Kugler, 1998.
  1103. Whitcup SM, Nussenblatt RB: Uveitis: Fundamentals and Clinical Practice. St. Louis, Mosby, 2005.
  1104. Boyd SR, Young S, Lightman S: Immunopathology of the noninfectious posterior and intermedi- ate uveitides. Surv Ophthalmol 2001;46:209-233.
  1105. Bouchenaki N, Cimino L, Auer C, Tao Tran V , Herbort CP: Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography. Klin Monatsbl Augenheilkd 2002;219:243-249.
  1106. Forrester JV: Autoimmunity and autoimmune disease of the eye. Dev Ophthalmol 1999;30:167-186.
  1107. Forrester JV , McMenamin PG: Immunopathogenic mechanisms in intraocular inflammation; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 159-185.
  1108. Elschnig A: Studien zur sympathischen Ophhalmis. Die antigene Wirkung des Augenpigmentes. Graefes Arch Ophthalmol 1910;76:509-546.
  1109. 9 Janeway CA Jr: The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today 1992;13:11-16.
  1110. Stuart JM, Townes AS, Kang AH: Collagen autoimmune arthritis. Annu Rev Immunol 1984;2: 199-218.
  1111. Wilder RL: Neuroendocrine-immune system interactions and autoimmunity. Annu Rev Immunol 1995;13:307-338.
  1112. Burkhardt H, Kalden JR: Animal models of autoimmune diseases. Rheumatol Int 1997;17:91-99.
  1113. Wacker WB: Proctor Lecture. Experimental allergic uveitis. Investigations of retinal auto- immunity and the immunopathologic responses evoked. Invest Ophthalmol Vis Sci 1991;32: 3119-3128.
  1114. Caspi RR: Immunogenetic aspects of clinical and experimental uveitis. Reg Immunol 1992;4: 321-330.
  1115. Caspi RR: Th1 and Th2 responses in pathogenesis and regulation of experimental autoimmune uveoretinitis. Int Rev Immunol 2002;21:197-208.
  1116. Crane IJ, Forrester JV: Th1 and Th2 lymphocytes in autoimmune disease. Crit Rev Immunol 2005;25:75-102.
  1117. Dick AD, Forrester JV, Liversidge J, Cope AP: The role of tumour necrosis factor (TNF-alpha) in experimental autoimmune uveoretinitis (EAU). Prog Retin Eye Res 2004;23:617-637.
  1118. Forrester JV, Liversidge J, Dua HS, Dick A, Harper F, McMenamin PG: Experimental autoim- mune uveoretinitis: a model system for immunointervention: a review. Curr Eye Res 1992; 11(suppl):33-40.
  1119. Yamaki K, Takiyama N, Itho N, Mizuki N, Seiya M, Sinsuke W, Hayakawa K, Kotani T: Experimentally induced Vogt-Koyanagi-Harada disease in two Akita dogs. Exp Eye Res 2005;80: 273-280.
  1120. Yamaki K, Gocho K, Hayakawa K, Kondo I, Sakuragi S: Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease. J Immunol 2000;165:7323-7329.
  1121. Bora NS, Sohn JH, Kang SG, Cruz JM, Nishihori H, Suk HJ, Wang Y, Kaplan HJ, Bora PS: Type I collagen is the autoantigen in experimental autoimmune anterior uveitis. J Immunol 2004;172: 7086-7094.
  1122. Deeg CA, Thurau SR, Gerhards H, Ehrenhofer M, Wildner G, Kaspers B: Uveitis in horses induced by interphotoreceptor retinoid-binding protein is similar to the spontaneous disease. Eur J Immunol 2002;32:2598-2606.
  1123. Deeg CA, Ehrenhofer M, Thurau SR, Reese S, Wildner G, Kaspers B: Immunopathology of recur- rent uveitis in spontaneously diseased horses. Exp Eye Res 2002;75:127-133.
  1124. Ichikawa T, Taguchi O, Takahashi T, Ikeda H, Takeuchi M, Tanaka T, Usui M, Nishizuka Y: Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus. Clin Exp Immunol 1991;86:112-117.
  1125. Egwuagu CE, Charukamnoetkanok P, Gery I: Thymic expression of autoantigens correlates with resistance to autoimmune disease. J Immunol 1997;159:3109-3112.
  1126. Takase H, Yu CR, Mahdi RM, Douek DC, Dirusso GB, Midgley FM, Dogra R, Allende G, Rosenkranz E, Pugliese A, Egwuagu CE, Gery I: Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals. Int Immunol 2005;17:1131-1140.
  1127. Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D: Projection of an immunological self shadow within the thymus by the AIRE protein. Science 2002;298:1395-1401.
  1128. Goldrath AW, Hedrick SM: Central tolerance matters. Immunity 2005;23:113-114.
  1129. Anderson MS, Venanzi ES, Chen Z, Berzins SP, Benoist C, Mathis D: The cellular mechanism of AIRE control of T cell tolerance. Immunity 2005;23:227-239.
  1130. Szpak Y, Vieville JC, Tabary T, Naud MC, Chopin M, Edelson C, Cohen JH, Dausset J, de Kozak Y, Pla M: Spontaneous retinopathy in HLA-A29 transgenic mice. Proc Natl Acad Sci USA 2001;98: 2572-2576.
  1131. Nussenblatt RB, Mittal KK, Ryan S, Green WR, Maumenee AE: Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune responsiveness to retinal S-antigen. Am J Ophthalmol 1982;94:147-158.
  1132. Ham DI, Kim SJ, Chen J, Vistica BP, Fariss RN, Lee RS, Wawrousek EF, Takase H, Yu CR, Egwuagu CE, Chan CC, Gery I: Central immunotolerance in transgenic mice expressing a foreign antigen under control of the rhodopsin promoter. Invest Ophthalmol Vis Sci 2004;45: 857-862. Zhang M, Vacchio MS, Vistica BP, Lesage S, Egwuagu CE, Yu CR, Gelderman MP, Kennedy MC, Wawrousek EF, Gery I: T cell tolerance to a neo-self antigen expressed by thymic epithelial cells: the soluble form is more effective than the membrane-bound form. J Immunol 2003;170: 3954-3962.
  1133. Gregerson DS, Dou C: Spontaneous induction of immunoregulation by an endogenous retinal antigen. Invest Ophthalmol Vis Sci 2002;43:2984-2991.
  1134. Gregerson DS, Xiao JJ: Failure of memory (CD44 high) CD4 T cells to recognize their target anti- gen in retina. J Neuroimmunol 2001;120:34-41.
  1135. McPherson SW, Roberts JP, Gregerson DS: Systemic expression of rat soluble retinal anti- gen induces resistance to experimental autoimmune uveoretinitis. J Immunol 1999;163: 4269-4276.
  1136. Gregerson DS, Torseth JW, McPherson SW, Roberts JP, Shinohara T, Zack DJ: Retinal expression of a neo-self antigen, beta-galactosidase, is not tolerogenic and creates a target for autoimmune uveoretinitis. J Immunol 1999;163:1073-1080.
  1137. Kapphahn RJ, Ethen CM, Peters EA, Higgins L, Ferrington DA: Modified alpha A crystallin in the retina: altered expression and truncation with aging. Biochemistry 2003;42:15310-15325.
  1138. Prendergast RA, Iliff CE, Coskuncan NM, Caspi RR, Sartani G, Tarrant TK, Lutty GA, McLeod DS: T cell traffic and the inflammatory response in experimental autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 1998;39:754-762.
  1139. Xu H, Forrester JV, Liversidge J, Crane IJ: Leukocyte trafficking in experimental autoimmune uveitis: breakdown of blood-retinal barrier and upregulation of cellular adhesion molecules. Invest Ophthalmol Vis Sci 2003;44:226-234.
  1140. Xu H, Manivannan A, Liversidge J, Sharp PF, Forrester JV, Crane IJ: Requirements for passage of T lymphocytes across non-inflamed retinal microvessels. J Neuroimmunol 2003;142:47-57.
  1141. Xu H, Manivannan A, Jiang HR, Liversidge J, Sharp PF, Forrester JV, Crane IJ: Recruitment of IFN-gamma-producing (Th1-like) cells into the inflamed retina in vivo is preferentially regulated by P-selectin glycoprotein ligand 1:P/E-selectin interactions. J Immunol 2004;172:3215-3224.
  1142. Jiang HR, Lumsden L, Forrester JV: Macrophages and dendritic cells in IRBP-induced experi- mental autoimmune uveoretinitis in B10RIII mice. Invest Ophthalmol Vis Sci 1999;40: 3177-3185.
  1143. Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, Gordon S: Macrophage receptors and immune recognition. Annu Rev Immunol 2005;23:901-944.
  1144. Robertson MJ, Erwig LP, Liversidge J, Forrester JV, Rees AJ, Dick AD: Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis. Invest Ophthalmol Vis Sci 2002;43:2250-2257.
  1145. Zhang M, Fukushima A, Vistica BP, Kim SJ, Hung L, Wawrousek EF, Egwuagu CE, Lee RS, Whitcup SM, Gery I: Skewed abrogation of tolerance to a neo self-antigen in double-transgenic mice coexpressing the antigen with interleukin-1␤ or interferon-␥. Cell Immunol 2001;207:6-12.
  1146. Jones LS, Rizzo LV, Agarwal RK, Tarrant TK, Chan CC, Wiggert B, Caspi RR: IFN-gamma- deficient mice develop experimental autoimmune uveitis in the context of a deviant effector response. J Immunol 1997;158:5997-6005.
  1147. Shao H, Fu Y, Liao T, Peng Y, Chen L, Kaplan HJ, Sun D: Anti-CD137 mAb treatment inhibits experimental autoimmune uveitis by limiting expansion and increasing apoptotic death of uveito- genic T cells. Invest Ophthalmol Vis Sci 2005;46:596-603.
  1148. Bagenstose LM, Agarwal RK, Silver PB, Harlan DM, Hoffmann SC, Kampen RL, Chan CC, Caspi RR: Disruption of CD40/CD40-ligand interactions in a retinal autoimmunity model results in protection without tolerance. J Immunol 2005;175:124-130.
  1149. Crane IJ, Xu H, Manivannan A, McKillop-Smith S, Lamont G, Wallace C, Liversidge J, Sharp PF, Forrester JV: Effect of anti-macrophage inflammatory protein-1␣ on leukocyte trafficking and disease progression in experimental autoimmune uveoretinitis. Eur J Immunol 2003;33:402-410.
  1150. Xu H, Manivannan A, Goatman KA, Liversidge J, Sharp PF, Forrester JV, Crane IJ: Improved leukocyte tracking in mouse retinal and choroidal circulation. Exp Eye Res 2002;74:403-410.
  1151. Xu H, Manivannan A, Liversidge J, Sharp PF, Forrester JV, Crane IJ: Involvement of CD44 in leukocyte trafficking at the blood-retinal barrier. J Leukoc Biol 2002;72:1133-1141.
  1152. Jiang HR, Muckersie E, Robertson M, Xu H, Liversidge J, Forrester JV: Secretion of interleukin-10 or interleukin-12 by LPS-activated dendritic cells is critically dependent on time of stimulus rela- tive to initiation of purified DC culture. J Leukoc Biol 2002;72:978-985.
  1153. Jiang HR, Muckersie E, Robertson M, Forrester JV: Antigen-specific inhibition of experimental autoimmune uveoretinitis by bone marrow-derived immature dendritic cells. Invest Ophthalmol Vis Sci 2003;44:1598-1607.
  1154. Gangi E, Vasu C, Cheatem D, Prabhakar BS: IL-10-producing CD4ϩ CD25ϩ regulatory T cells play a critical role in granulocyte-macrophage colony-stimulating factor-induced suppression of experimental autoimmune thyroiditis. J Immunol 2005;174:7006-7013.
  1155. Li Y, Heuser JS, Kosanke SD, Hemric M, Cunningham MW: Protection against experimental autoimmune myocarditis is mediated by interleukin-10-producing T cells that are controlled by dendritic cells. Am J Pathol 2005;167:5-15.
  1156. Mahnke K, Enk AH: Dendritic cells: key cells for the induction of regulatory T cells? Curr Top Microbiol Immunol 2005;293:133-150.
  1157. Agarwal RK, Kang Y, Zambidis E, Scott DW, Chan CC, Caspi RR: Retroviral gene therapy with an immunoglobulin-antigen fusion construct protects from experimental autoimmune uveitis. J Clin Invest 2000;106:245-252.
  1158. Oksala A: The significance of treatment by antibiotics and steroids in acute anterior uveitis. Acta Ophthalmol (Copenh) 1960;38:405-409.
  1159. Campbell FP: Retina and optic nerve. Arch Ophthalmol 1968;79:789-802.
  1160. Dick AD, Kreutzer B, Laliotou B, Forrester JV: Phenotypic analysis of retinal leukocyte infiltration during combined cyclosporin A and nasal antigen administration of retinal antigens: delay and inhi- bition of macrophage and granulocyte infiltration. Ocul Immunol Inflamm 1997;5:129-140.
  1161. Mochizuki M, Kawashima H: Effects of FK506, 15-deoxyspergualin, and cyclosporine on experi- mental autoimmune uveoretinitis in the rat. Autoimmunity 1990;8:37-41.
  1162. Caspi RR, McAllister CG, Gery I, Nussenblatt RB: Differential effects of cyclosporins A and G on functional activation of a T-helper-lymphocyte line mediating experimental autoimmune uveore- tinitis. Cell Immunol 1988;113:350-360.
  1163. Liversidge J, Thomson AW, Sewell HF, Forrester JV: EAU in the guinea pig: inhibition of cell- mediated immunity and Ia antigen expression by cyclosporin A. Clin Exp Immunol 1987;69: 591-600.
  1164. Murphy CC, Greiner K, Plskova J, Duncan L, Frost NA, Forrester JV, Dick AD: Cyclosporine vs tacrolimus therapy for posterior and intermediate uveitis. Arch Ophthalmol 2005;123:634-641.
  1165. Dick AD, Meyer P, James T, Forrester JV, Hale G, Waldmann H, Isaacs JD: Campath-1H therapy in refractory ocular inflammatory disease. Br J Ophthalmol 2000;84:107-109.
  1166. Greiner K, Murphy CC, Willermain F, Duncan L, Plskova J, Hale G, Isaacs JD, Forrester JV, Dick AD: Anti-TNF␣ therapy modulates the phenotype of peripheral blood CD4ϩ T cells in patients with posterior segment intraocular inflammation. Invest Ophthalmol Vis Sci 2004;45:170-176.
  1167. Murphy CC, Greiner K, Plskova J, Duncan L, Frost A, Isaacs JD, Rebello P, Waldmann H, Hale G, Forrester JV, Dick AD: Neutralizing tumor necrosis factor activity leads to remission in patients with refractory noninfectious posterior uveitis. Arch Ophthalmol 2004;122:845-851.
  1168. Kotter I, Zierhut M, Eckstein AK, Vonthein R, Ness T, Gunaydin I, Grimbacher B, Blaschke S, Meyer-Riemann W, Peter HH, Stubiger N: Human recombinant interferon alfa-2a for the treat- ment of Behçet's disease with sight threatening posterior or panuveitis. Br J Ophthalmol 2003;87: 423-431.
  1169. Plskova J, Greiner K, Muckersie E, Duncan L, Forrester JV: Interferon-alpha: a key factor in autoimmune disease? Invest Ophthalmol Vis Sci 2006;47:3946-3950.
  1170. Kotter I, Deuter C, Stubiger N, Zierhut M: Interferon-␣ (IFN-␣) application versus tumor necrosis factor-␣ antagonism for ocular Behçet's disease: focusing more on IFN. J Rheumatol 2005;32: 1633-1634.
  1171. Jabs DA, Nussenblatt RB, Rosenbaum JT: Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 2005;140:509-516. References
  1172. Urayama A, Yamada N, Susaki T, Nishiyama Y, Watanabe N, Wakusawa S, Satoh Y: Unilateral acute uveitis with retinal periarteritis and detachment. Jpn J Clin Ophthalmol 1971;25:607-619.
  1173. Friberg TR, Jost BF: Acute retinal necrosis in an immunosuppressed patient. Am J Ophthalmol 1984;98:515-517.
  1174. Culbertson WW , Atherton SS: Acute retinal necrosis and similar retinitis syndromes. Int Ophthalmol Clin 1993;33:129-143.
  1175. Sellitti TP , Huang AJ, Schiffman J, Davis JL: Association of herpes zoster ophthalmicus with acquired immunodeficiency syndrome and acute retinal necrosis. Am J Ophthalmol 1993;116: 297-301.
  1176. Cunningham ET Jr, Short GA, Irvine AR, Duker JS, Margolis TP: Acquired immunodeficiency syndrome-associated herpes simplex virus retinitis. Clinical description and use of a polymerase chain reaction-based assay as a diagnostic tool. Arch Ophthalmol 1996;114:834-840.
  1177. Price FW , Schlaegel TF: Bilateral acute retinal necrosis. Am J Ophthalmol 1980;89:419-424.
  1178. Gartry DS, Spalton DJ, Tilzey A, Hykin PG: Acute retinal necrosis syndrome. Br J Ophthalmol 1991;75:292-297.
  1179. Falcone PM, Brockhurst RJ: Delayed onset of bilateral acute retinal necrosis syndrome: a 34-year interval. Ann Ophthalmol 1993;25:373-374.
  1180. 9 Ezra E, Pearson R V , Etchells DE, Gregor ZJ: Delayed fellow eye involvement in acute retinal necrosis syndrome. Am J Ophthalmol 1995;120:115-117.
  1181. Schlingemann RO, Bruinenberg M, Wertheim-van Dillen P, Feron E: Twenty years' delay of fellow eye involvement in herpes simplex virus type 2-associated bilateral acute retinal necrosis syn- drome. Am J Ophthalmol 1996;122:891-892.
  1182. Ganatra JB, Chandler D, Santos C, Kuppermann B, Margolis TP: Viral causes of the acute retinal necrosis syndrome. Am J Ophthalmol 2000;129:166-172.
  1183. Culbertson WW, Blumenkranz MS, Haines H, Gass DM, Mitchell KB, Norton EW: The acute reti- nal necrosis syndrome. Part 2: Histopathology and etiology. Ophthalmology 1982;89:1317-1325.
  1184. Culbertson WW, Blumenkranz MS, Pepose JS, Stewart JA, Curtin VT: Varicella zoster virus is a cause of the acute retinal necrosis syndrome. Ophthalmology 1986;93:559-569.
  1185. Levinson RD, Reidy R, Chiu MT: Acute retinal necrosis after neonatal herpes encephalitis. Br J Ophthalmol 1999;83:123.
  1186. Van Gelder RN, Willig JL, Holland GN, Kaplan HJ: Herpes simplex virus type 2 as a cause of acute retinal necrosis syndrome in young patients. Ophthalmology 2001;108:869-876.
  1187. Tan JCH, Byles D, Stanford MR, Frith PA, Graham EM: Acute retinal necrosis in children caused by herpes simplex virus. Retina 2001;21:344-347.
  1188. Landry ML, Mullangi P, Nee P, Klein BR: Herpes simplex virus type 2 acute retinal necrosis 9 years after neonatal herpes. J Pediatr 2005;146:836-838.
  1189. Silverstein BE, Conrad D, Margolis TP, Wong IG: Cytomegalovirus-associated acute retinal necro- sis syndrome. Am J Ophthalmol 1997;123:257-258.
  1190. Tran TH, Rozenberg F, Cassoux N, Rao NA, Lehoang P, Bodaghi B: Polymerase chain reaction analysis of aqueous humour samples in necrotising retinitis. Br J Ophthalmol 2003;87:79-83.
  1191. Fisher JP, Lewis ML, Blumenkranz MS, Culbertson WW, Flynn HW Jr, Clarkson JG, Gass JD, Norton EW: The acute retinal necrosis syndrome. Part I. Clinical manifestations. Ophthalmology 1982;89:1309-1316.
  1192. Opremcak EM: Uveitis. A Clinical Manual for Ocular Inflammation, ed 1. New York, Springer, 1995, pp 115-117.
  1193. Usui N: Acute retinal necrosis. Atarasii Gannka 2003;20:309-320.
  1194. Culbertson WW, Dix RD: Varicella-zoster virus disease: posterior segment of the eye; in Pepose JS, Holland GN, Wilhelmus KR (eds): Ocular Infection and Immunity. St. Louis, Mosby, 1996, pp 1131-1149.
  1195. Margolis TP, Atherton SS: Herpes simplex virus diseases: posterior segment of the eye; in Pepose JS, Holland GN, Wilhelmus KR (eds): Ocular Infection and Immunity. St. Louis, Mosby, 1996, pp 1155-1167.
  1196. Holland GN: Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. Am J Ophthalmol 1994;117:663-667.
  1197. Witmer R: Clinical implications of aqueous humor studies in uveitis. Am J Ophthalmol 1978;86:39-45.
  1198. Okitsu Y: Diagnostic value of antibody titer and quotient of herpes viruses in intraocular fluids. Jpn J Clin Ophthalmol 1988;42:801-805.
  1199. Usui M, Usui N, Goto H, Minoda H, Rai T: Polymerase chain reaction for diagnosis of herpetic intraocular inflammation. Ocul Immunol Inflamm 1993;1:105-112.
  1200. Knox CM, Chandler D, Short GA, Margolis TP: Polymerase chain reaction-based assay of vitre- ous samples for the diagnosis of viral retinitis. Use in diagnostic dilemmas. Ophthalmology 1998;105:37-44.
  1201. Asano S, Yoshikawa T, Kimura H, Enomoto Y, Ohashi M, Terasaki H, Nishiyama Y: Monitoring herpesvirus DNA in three cases of acute retinal necrosis by real-time PCR. J Clin Virol 2004;29:206-209.
  1202. Bonfioli AA, Eller AW: Acute retinal necrosis. Semin Ophthalmol 2005;20:155-160. von Szily A: Experimental endogenous transmission of infection from bulbus to bulbus. Klin Monatsbl Augenheilkd 1924;72:593-602.
  1203. Whittum JA, McCulley JP, Niederkorn JY, Streilein JW: Ocular disease induced in mice by ante- rior chamber inoculation of herpes simplex virus. Invest Ophthalmol Vis Sci 1984;25:1065-1073.
  1204. Whittum JA, Niederkorn JY, McCulley JP, Streilein JW: Intracameral inoculation of herpes sim- plex virus type 1 induces anterior chamber associated immune deviation. Curr Eye Res 1983;2:691-697.
  1205. Vann VR, Atherton SS: Neural spread of herpes simplex virus after anterior chamber inoculation. Invest Ophthalmol Vis Sci 1990;32:2462-2472.
  1206. Azumi A, Atherton SS: Sparing of the ipsilateral retina following anterior chamber inoculation of HSV-1: requirement for either CD4 ϩ or CD8 ϩ T cells. Invest Ophthalmol Vis Sci 1994;34: 3251-3259.
  1207. Matsubara S, Atherton SS: Spread of HSV-1 to the suprachiasmatic nuclei and retina in T cell depleted BALB/c mice. J Neuroimmunol 1997;80:165-171.
  1208. Rochat C, Polla BS, Herbort CP: Immunological profiles in patients with acute retinal necrosis. Graefes Arch Clin Exp Ophthalmol 1996;234:547-552.
  1209. Kezuka T, Sakai J, Usui N, Streilein JW, Usui M: Evidence for antigen-specific immune deviation in patients with acute retinal necrosis. Arch Ophthalmol 2001;119:1044-1049.
  1210. Kezuka T: Immune deviation and ocular infections with varicella zoster virus. Ocul Immunol Inflamm 2004;12:17-24.
  1211. Friedlander SM, Rahhal FM, Ericson L, Friedlander SM, Rahhal FM, Ericson L, Arevalo JF, Hughes JD, Levi L, Wiley CA, Graham EM, Freeman WR: Optic neuropathy preceding acute reti- nal necrosis in acquired immunodeficiency syndrome. Arch Ophthalmol 1996;114:1481-1485.
  1212. Shayegani A, Odel JG, Kazim M, Hall LS, Bamford N, Schubert H: Varicella-zoster virus retro- bulbar optic neuritis in a patient with human immunodeficiency virus. Am J Ophthalmol 1996;122: 586-588.
  1213. Tornerup NR, Fomagaard A, Nielson NV: HSV-1-induced acute retinal necrosis syndrome pre- senting with severe inflammatory orbitopathy, proptosis, and optic nerve involvement. Ophthal- mology 2000;107:397-401.
  1214. Maertzdorf J, Van der Lelij A, Baarsma GS, Osterhaus AD, Verjans GM: Herpes simplex virus type 1 (HSV-1)-induced retinitis following herpes simplex encephalitis: indication for brain-to-eye transmission of HSV-1. Ann Neurol 2001;49:104-106.
  1215. Takasu T, Furuta Y, Sato KC, Fukuda S, Inuyama Y, Nagashima K: Detection of latent herpes sim- plex virus DNA and RNA in human geniculate ganglia by the polymerase chain reaction. Acta Otolaryngol 1992;112:1004-1011.
  1216. Mahalingam R, Wellish MC, Dueland AN, Cohrs RJ, Gilden DH: Localization of herpes simplex virus and varicella zoster virus DNA in human ganglia. Ann Neurol 1992;31:444-448.
  1217. Baringer JR, Pisani P: Herpes simplex virus genome in human nervous system tissue analyzed by polymerase chain reaction. Ann Neurol 1994;36:823-829.
  1218. Bustos DE, Atherton SS: Detection of herpes simplex virus type 1 in human ciliary ganglia. Invest Ophthalmol Vis Sci 2002;43:2244-2249.
  1219. Dr. Sally S. Atherton Department of Cellular Biology and Anatomy Medical College of Georgia, R and E Building, CB2915
  1220. Augusta, GA 30912 (USA)
  1221. Tel. ϩ1 706 721 3731, Fax ϩ1 706 721 6120, E-Mail satherton@mail.mcg.edu References
  1222. Pearlman E, Toe L, Boatin BA, Gilles AA, Higgins AW, Unnasch TR: Eotaxin expression in Onchocerca volvulus-induced dermatitis after topical application of diethylcarbamazine. J Infect Dis 1999;180:1394-1397.
  1223. Maizels RM, Balic A, Gomez-Escobar N, Nair M, Taylor MD, Allen JE: Helminth parasites -mas- ters of regulation. Immunol Rev 2004;201:89-116.
  1224. Goodridge HS, Wilson EH, Harnett W , Campbell CC, Harnett MM, Liew FY: Modulation of macrophage cytokine production by ES-62, a secreted product of the filarial nematode Acanthocheilonema viteae. J Immunol 2001;167:940-945.
  1225. Ottesen EA, Weller PF , Heck L: Specific cellular immune unresponsiveness in human filariasis. Immunology 1977;33:413-421.
  1226. Brattig NW: Pathogenesis and host responses in human onchocerciasis: impact of Onchocerca filariae and Wolbachia endobacteria. Microbes Infect 2004;6:113-128.
  1227. Steel C, Nutman TB: CTLA-4 in filarial infections: implications for a role in diminished T cell reactivity. J Immunol 2003;170:1930-1938.
  1228. Doetze A, Satoguina J, Burchard G, Rau T, Loliger C, Fleischer B, Hoerauf A: Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by T h 3/T r 1-type cytokines IL-10 and transforming growth factor-␤ but not by a T h 1 to T h 2 shift. Int Immunol 2000;12:623-630.
  1229. Hoerauf A, Satoguina J, Saeftel M, Specht S: Immunomodulation by filarial nematodes. Parasite Immunol 2005;27:417-429.
  1230. Taylor MD, LeGoff L, Harris A, Malone E, Allen JE, Maizels RM: Removal of regulatory T cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo. J Immunol 2005;174:4924-4933.
  1231. Kozek WJ, Marroquin HF: Intracytoplasmic bacteria in Onchocerca volvulus. Am J Trop Med Hyg 1977;26:663-678.
  1232. Taylor MJ, Hoerauf A: A new approach to the treatment of filariasis (comment). Curr Opin Infect Dis 2001;14:727-731.
  1233. Taylor MJ, Bilo K, Cross HF, Archer JP, Underwood AP: 16S rDNA phylogeny and ultrastructural characterization of Wolbachia intracellular bacteria of the filarial nematodes Brugia malayi, B. pahangi, and Wuchereria bancrofti. Exp Parasitol 1999;91:356-361.
  1234. McGarry HF, Egerton GL, Taylor MJ: Population dynamics of Wolbachia bacterial endosymbionts in Brugia malayi. Mol Biochem Parasitol 2004;135:57-67.
  1235. Taylor M: One in the eye for river blindness. Trends Parasitol 2001;17:358.
  1236. Hoerauf A, Mand S, Adjei O, Fleischer B, Buttner DW: Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Lancet 2001;357:1415-1416.
  1237. Hoerauf A, Mand S, Volkmann L, Buttner M, Marfo-Debrekyei Y, Taylor M, Adjei O, Buttner DW: Doxycycline in the treatment of human onchocerciasis: kinetics of Wolbachia endobacteria reduc- tion and of inhibition of embryogenesis in female Onchocerca worms. Microbes Infect 2003;5: 261-273.
  1238. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A: Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo- controlled trial. Lancet 2005;365:2116-2121.
  1239. Cross HF, Haarbrink M, Egerton G, Yazdanbakhsh M, Taylor MJ: Severe reactions to filarial chemotherapy and release of Wolbachia endosymbionts into blood (comment). Lancet 2001;358: 1873-1875.
  1240. Keiser PB, Reynolds SM, Awadzi K, Ottesen EA, Taylor MJ, Nutman TB: Bacterial endosym- bionts of Onchocerca volvulus in the pathogenesis of posttreatment reactions. J Infect Dis 2002;185:805-811.
  1241. Brattig NW, Buttner DW, Hoerauf A: Neutrophil accumulation around Onchocerca worms and chemotaxis of neutrophils are dependent on Wolbachia endobacteria. Microbes Infect 2001;3: 439-446.
  1242. Taylor MJ, Cross HF, Bilo K: Inflammatory responses induced by the filarial nematode Brugia malayi are mediated by lipopolysaccharide-like activity from endosymbiotic Wolbachia bacteria. J Exp Med 2000;191:1429-1436.
  1243. Pearlman E: Experimental onchocercal keratitis. Parasitol Today 1996;12:261-267.
  1244. Hoerauf A, Buttner DW, Adjei O, Pearlman E: Onchocerciasis. BMJ 2003;326:207-210.
  1245. Chakravarti B, Herring TA, Lass JH, Parker JS, Bucy RP, Diaconu E, Tseng J, Whitfield DR, Greene BM, Chakravarti DN: Infiltration of CD4ϩ T cells into cornea during development of Onchocerca volvulus-induced experimental sclerosing keratitis in mice. Cell Immunol 1994;159: 306-314.
  1246. Chakravarti B, Lass JH, Bardenstein DS, Diaconu E, Roy CE, Herring TA, Chakravarti DN, Greene BM: Immune-mediated Onchocerca volvulus sclerosing keratitis in the mouse. Exp Eye Res 1993;57:21-27.
  1247. Chakravarti B, Lagoo-Deenadayalan S, Parker JS, Whitfield DR, Lagoo A, Chakravarti DN: In vivo molecular analysis of cytokines in a murine model of ocular onchocerciasis. I. Up-regulation of IL-4 and IL-5 mRNAs and not IL-2 and IFN gamma mRNAs in the cornea due to experimental interstitial keratitis. Immunol Lett 1996;54:59-64.
  1248. Hall LR, Pearlman E: Pathogenesis of onchocercal keratitis (river blindness). Clin Microbiol Rev 1999;12:445-453.
  1249. Pearlman E, Lass JH, Bardenstein DS, Kopf M, Hazlett FE Jr, Diaconu E, Kazura JW: Interleukin 4 and T helper type 2 cells are required for development of experimental onchocercal keratitis (river blindness). J Exp Med 1995;182:931-940.
  1250. Hall LR, Diaconu E, Pearlman E: A dominant role for Fc gamma receptors in antibody-dependent corneal inflammation. J Immunol 2001;167:919-925.
  1251. Hall LR, Lass JH, Diaconu E, Strine ER, Pearlman E: An essential role for antibody in neutrophil and eosinophil recruitment to the cornea: B cell-deficient (MT) mice fail to develop Th2-dependent, helminth-mediated keratitis. J Immunol 1999;163:4970-4975.
  1252. Hall LR, Diaconu E, Patel R, Pearlman E: CXC chemokine receptor 2 but not C-C chemokine receptor 1 expression is essential for neutrophil recruitment to the cornea in helminth-mediated keratitis (river blindness). J Immunol 2001;166:4035-4041.
  1253. Kaifi JT, Diaconu E, Pearlman E: Distinct roles for PECAM-1, ICAM-1, and VCAM-1 in recruit- ment of neutrophils and eosinophils to the cornea in ocular onchocerciasis (river blindness). J Immunol 2001;166:6795-6801.
  1254. Kaifi JT, Hall LR, Diaz C, Sypek J, Diaconu E, Lass JH, Pearlman E: Impaired eosinophil recruit- ment to the cornea in P-selectin-deficient mice in Onchocerca volvulus keratitis (river blindness). Invest Ophthalmol Vis Sci 2000;41:3856-3861.
  1255. Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P: Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J Exp Med 1997;185:785-790. Saint Andre A, Blackwell NM, Hall LR, Hoerauf A, Brattig NW, Volkmann L, Taylor MJ, Ford L, Hise AG, Lass JH, Diaconu E, Pearlman E: The role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness. Science 2002;295:1892-1895.
  1256. Gillette-Ferguson I, Hise AG, McGarry HF, Turner J, Esposito A, Sun Y, Diaconu E, Taylor MJ, Pearlman E: Wolbachia-induced neutrophil activation in a mouse model of ocular onchocerciasis (river blindness). Infect Immun 2004;72:5687-5692.
  1257. Takeda K, Akira S: Toll receptors and pathogen resistance. Cell Microbiol 2003;5:143-153.
  1258. Takeda K, Kaisho T, Akira S: Toll-like receptors. Annu Rev Immunol 2003;21:335-376.
  1259. Brattig NW, Bazzocchi C, Kirschning CJ, Reiling N, Buttner DW, Ceciliani F, Geisinger F, Hochrein H, Ernst M, Wagner H, Bandi C, Hoerauf A: The major surface protein of Wolbachia endosymbionts in filarial nematodes elicits immune responses through TLR2 and TLR4. J Immunol 2004;173:437-445.
  1260. Blaxter M, Daub J, Guiliano D, Parkinson J, Whitton C: The Brugia malayi genome project: expressed sequence tags and gene discovery. Trans R Soc Trop Med Hyg 2002;96:7-17.
  1261. Gillette-Ferguson I, Hise AG, Sun Y, Diaconu E, McGarry HF, Taylor MJ, Pearlman E: Wolbachia and Onchocerca volvulus-induced keratitis (river blindness) is dependent on myeloid differentia- tion factor 88 (MyD88). Infect Immun 2006;74:2442-2445.
  1262. Johnson AC, Heinzel FP, Diaconu E, Sun Y, Hise AG, Golenbock D, Lass JH, Pearlman E: Activation of Toll-like receptor (TLR)2, TLR4, and TLR9 in the mammalian cornea induces MyD88-dependent corneal inflammation. Invest Ophthalmol Vis Sci 2005;46:589-595.
  1263. Song PI, Abraham TA, Park Y, Zivony AS, Harten B, Edelhauser HF, Ward SL, Armstrong CA, Ansel JC: The expression of functional LPS receptor proteins CD14 and Toll-like receptor 4 in human corneal cells. Invest Ophthalmol Vis Sci 2001;42:2867-2877.
  1264. Zhang J, Xu K, Ambati B, Yu FS: Toll-like receptor 5-mediated corneal epithelial inflammatory responses to Pseudomonas aeruginosa flagellin. Invest Ophthalmol Vis Sci 2003;44:4247-4254.
  1265. Cubitt CL, Tang Q, Monteiro CA, Lausch RN, Oakes JE: IL-8 gene expression in cultures of human corneal epithelial cells and keratocytes. Invest Ophthalmol Vis Sci 1993;34:3199-3206.
  1266. Hayashi F, Means TK, Luster AD: Toll-like receptors stimulate human neutrophil function. Blood 2003;102:2660-2669. References
  1267. Miller JJ, Scott IU, Flynn HW , Smiddy WE, Newton J, Miller D: Acute-onset endophthalmitis after cataract surgery (2000-2004): incidence, clinical settings, and visual acuity outcomes after treat- ment. Am J Ophthalmol 2005;139:983-987.
  1268. Taban M, Behrens A, Newcomb RL, Nobe MY , Saedi G, Sweet PM, McDonnell PJ: Acute endophthalmitis following cataract surgery: a systematic review of the literature. Arch Ophthalmol 2005;123:613-620.
  1269. Recchia FM, Busbee BG, Pearlman RB, Carvalho-Recchia CA, Ho AC: Changing trends in the microbiologic aspects of postcataract endophthalmitis. Arch Ophthalmol 2005;123:341-346.
  1270. Mandelbaum S, Foster RK: Exogenous endophthalmitis; in Pepose JS, Holland GN, Wilhelms KR (eds): Ocular Infection and Immunity. St. Louis, Mosby, 1996, pp 1298-1320.
  1271. Essex R W , Yi Q, Charles PG, Allen PJ: Post-traumatic endophthalmitis. Ophthalmology 2004;111: 2015-2022.
  1272. Schiedler V , Scott IU, Flynn HW Jr, Davis JL, Benz MS, Miller D: Culture-proven endogenous endophthalmitis: clinical features and visual acuity outcomes. Am J Ophthalmol 2004;137: 725-731.
  1273. Callegan MC, Kane ST, Cochran DC, Gilmore MS: Molecular mechanisms of Bacillus endo- phthalmitis pathogenesis. DNA Cell Biol 2002;21367-21373.
  1274. Callegan MC, Kane ST, Cochran C, Novosad B, Gilmore MS, Gominet M, Lereclus D: Bacillus endophthalmitis: roles of bacterial toxins and motility during infection. Invest Ophthalmol Vis Sci 2005;46:3233-3238.
  1275. Callegan MC, Cochran DC, Kane ST, Gilmore MS, Gominet M, Lereclus D: Contribution of membrane-damaging toxins to Bacillus endophthalmitis pathogenesis. Infect Immun 2002;70: 5381-5389.
  1276. Callegan MC, Engelbert M, Parke DW 2nd, Jett BD, Gilmore MS: Bacterial endophthalmitis: epi- demiology, therapeutics, and bacterium-host interactions. Clin Microbiol Rev 2002;15:111-124.
  1277. Perkins SL, Han DP, Burke JM, Schlievert PM, Wirostko WJ, Tarasewicz DG, Skumatz CM: Intravitreally injected human immunoglobulin attenuates the effects of Staphylococcus aureus culture supernatant in a rabbit model of toxin-mediated endophthalmitis. Arch Ophthalmol 2004;122: 1499-1506.
  1278. Dajcs JJ, Thibodeaux BA, Girgis DO, Shaffer MD, Delvisco SM, O'Callaghan RJ: Immunity to lysostaphin and its therapeutic value for ocular MRSA infections in the rabbit. Invest Ophthalmol Vis Sci 2002;43:3712-3716.
  1279. Scott IU, Loo RH, Flynn HW Jr, Miller D: Endophthalmitis caused by Enterococcus faecalis: antibiotic selection and treatment outcomes. Ophthalmology 2003;110:1573-1577.
  1280. Jett BD, Jensen JG, Atkuri RV, Gilmore MS: Evaluation of therapeutic measures for treating endophthalmitis caused by isogenic toxin-producing and toxin-nonproducing Enterococcus fae- calis strains. Invest Ophthalmol Vis Sci 1995;36:9-15.
  1281. Engelbert M, Mylonakis E, Ausubel FM, Calderwood SB, Gilmore MS: Contribution of gelati- nase, serine protease, and fsr to the pathogenesis of Enterococcus faecalis endophthalmitis. Infect Immun 2004;72:3628-3633.
  1282. Aldave AJ, Stein JD, Deramo VA, Shah GK, Fischer DH, Maguire JI: Treatment strategies for postoperative Propionibacterium acnes endophthalmitis. Ophthalmology 1999;106:2395-2401.
  1283. Chen YJ, Kuo HK, Wu PC, Kuo ML, Tsai HH, Liu CC, Chen CH: A 10-year comparison of endogenous endophthalmitis outcomes: an east Asian experience with Klebsiella pneumoniae infection. Retina 2004;24:383-390.
  1284. Ma LC, Fang CT, Lee CZ, Shun CT, Wang JT: Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection. J Infect Dis 2005;192:117-128.
  1285. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:879-889.
  1286. Webster G, Leyden JJ, Musson RA, Douglas SD: Susceptibility of Propionibacterium acnes to killing and degradation by human neutrophils and monocytes in vitro. Infect Immun 1985;49: 116-121.
  1287. Kwon B, Hazlett LD: Association of CD4ϩ T cell-dependent keratitis with genetic susceptibility to Pseudomonas aeruginosa ocular infection. J Immunol 1997;159:6283-6290.
  1288. Engstrom RE, Modino BJ, Glasgow BJ, Pitchekian-Halabi H, Adamu SA: Immune response to Staphylococcus aureus endophthalmitis in a rabbit model. Invest Ophthalmol Vis Sci 1991;32: 1523-1533.
  1289. Maylath FR, Leopold JH: Study of experimental ocular infection. Am J Ophthalmol 1955;40:86-101.
  1290. Haynes RJ, McElveen JE, Dua HS, Tighe PJ, Liversidge J: Expression of human beta-defensins in intraocular tissues. Invest Ophthalmol Vis Sci 2000;41:3026-3031.
  1291. Beyer TL, Vogler G, Sharma D, O'Donnell FE Jr: Protective barrier effect of the posterior lens capsule in exogenous bacterial endophthalmitis: an experimental primate study. Invest Ophthalmol Vis Sci 1984;25:108-112.
  1292. Takeda K, Akira S: Toll-like receptors in innate immunity. Int Immunol 2005;17:1-14.
  1293. Kumr V, Nagineni CN, Chin MS, Hooks JJ, Detrick B: Innate immunity in the retina: Toll-like recep- tor (TLR) signaling in human retinal pigment epithelial cells. J Neuroimmunol 2004;153:7-15.
  1294. Tosi MF: Innate immune responses to infection. J Allergy Clin Immunol 2005;116:241-249.
  1295. Engelbert M, Gilmore MS: Fas ligand but not complement is critical for control of experimental Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 2005;46:2479-2486.
  1296. Giese MJ, Sumner HL, Berliner JA, Mondino BJ: Cytokine expression in a rat model of Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 1998;39:2785-2790.
  1297. Giese MJ, Shum DC, Rayner SA, Mondino BJ, Berliner JA: Adhesion molecule expression in a rat model of Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 2000;41:145-153.
  1298. Griffith T, Brunner T, Fletcher SM, Green DR, Ferguson TA: Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189-1192.
  1299. Gregory MS, Repp AC, Hohlbaum AM, Saff RR, Marshak-Rothstein A, Ksander BR: Membrane Fas ligand activates innate immunity and terminates ocular immune privilege. J Immunol 2002;169:2727-2735.
  1300. Meredith TA, Aguilar HE, Drews C, Sawant A, Gardner S, Wilson LA, Grossniklaus HE: Intraocular dexamethasone produces a harmful effect on treatment of experimental Staphylococcus aureus endophthalmitis. Trans Am Ophthalmol Soc 1996;94:241-257.
  1301. Shah GK, Stein JD, Sharma S, Sivalingam A, Benson WE, Regillo CD, Brown GC, Tasman W: Visual outcomes following the use of intravitreal steroids in the treatment of postoperative endophthalmitis. Am Acad Ophthalmol 2000;107:486-489.
  1302. Dr. M. Gilmore Schepens Eye Research Institute 20 Staniford Street Boston, MA 02114 (USA)
  1303. Tel. ϩ1 617 912 7448, Fax ϩ1 617 912 0115, E-Mail mgilmore@vision.eri.harvard.edu Niederkorn JY, Kaplan HJ (eds): Immune Response and the Eye. Chem Immunol Allergy. Basel, Karger, 2007, vol 92, pp 276-289 References
  1304. Ehrlich P: Ueber den jetzigen Stand der Karzinomforschung. Ned Tijdschr Geneeskd 1909;5: 273-290.
  1305. Thomas L: Reactions to homologous tissue antigens in relation to hypersensitivity; in Lawrence HS (ed): Cellular and Humoral Aspects of the Hypersensitive States. New York, Hoeber-Harper, 1959, pp 529-532.
  1306. Burnet FM: Immunological factors in the process of carcinogenesis. Br Med Bull 1964;20:154-158.
  1307. Old LJ, Boyse EA: Specific antigens of tumors and leukemias of experimental animals. Med Clin North Am 1966;50:901-912.
  1308. Klein G: Tumor antigens. Annu Rev Microbiol 1966;20:223-252.
  1309. Stutman O: Tumor development after 3-methylcholanthrene in immunologically deficient athymic- nude mice. Science 1974;183:534-536.
  1310. Herberman RB, Holden HT: Natural cell-mediated immunity. Adv Cancer Res 1978;27:305-377.
  1311. Dighe AS, Richards E, Old LJ, Schreiber RD: Enhanced in vivo growth resistance to rejection of tumor cells expressing dominant negative IFN␥ receptors. Immunity 1994;1:447-456.
  1312. Kaplan DH, Shankaran V , Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD: Demonstration of an interferon ␥-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 1998;95:7556-7561.
  1313. Street SE, Trapani JA, MacGregor D, Smyth MJ: Suppression of lymphoma and epithelial malig- nancies effected by interferon ␥. J Exp Med 1998;196:129-134.
  1314. van den Broek MF, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutza WK, Melief CJM, Zinkernagel RM, Hengartner H: Decreased tumor surveillance in perforin-deficient mice. J Exp Med 1996;184:1781-1790.
  1315. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD: IFN␥ and lym- phocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001;410: 1107-1111.
  1316. Smyth MJ, Crowe NY, Godfrey DI: NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 2001;13:459-463.
  1317. Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R, Hobby P, Sutton B, Tigelaar RE, Hayday AC: Regulation of cutaneous malignancy by ␥␦ T cells. Science 2001;294:605-609.
  1318. Nacht M, Jacks T: V(D)J recombination is not required for the development of lymphoma in p53- deficient mice. Cell Growth Differ 1998;9:131-138.
  1319. Liao MJ, Zhang XX, Hill R, Gao J, Qumsiyeh MB, Nichols W, Van Dyke T: No requirement for V(D)J recombination in p53-deficient thymic lymphoma. Mol Cell Biol 1998;18:3495-3501.
  1320. Diefenbach A, Raulet DH: Innate immune recognition by stimulatory immunoreceptors. Curr Opin Immunol 2003;15:37-44.
  1321. Brandlein S, Pohle T, Ruoff N, Wozniak E, Muller-Hermelink HK, Vollmers HP: Natural IgM anti- bodies and immunosurveillance mechanisms against epithelial cancer cells in humans. Cancer Res 2003;63:7995-8005.
  1322. Algarra I, Ohlen C, Perez M, Ljunggren HG, Klein G, Garrido F, Karre K: NK sensitivity and lung clearance of MHC-class-I-deficient cells within a heterogeneous fibrosarcoma. Int J Cancer 1989;44:675-680.
  1323. Vetter CS, Groh V, thorStraten P, Spies T, Brocker EB, Becker JC: Expression of stress-induced MHC class I related chain molecules on human melanoma. J Invest Dermatol 2002;118:600-605.
  1324. Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T: Broad tumor-associated expres- sion and recognition by tumor-derived ␥␦ T cells of MICA and MICB. Proc Natl Acad Sci USA 1999;96:6879-6884.
  1325. Gilfillan S, Ho EL, Cella M, Yokoyama WM, Colonna M: NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation. Nat Immunol 2002;3:1150-1155.
  1326. Salih HR, Rammensee HG, Steinle A: Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J Immunol 2002;169:4098-4102.
  1327. Taniguchi M, Seino K, Nakayama T: The NKT cell system: bridging innate and acquired immu- nity. Nat Immunol 2003;4:1164-1165.
  1328. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY, Godfrey DI: Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 2000;191:661-668.
  1329. Crowe NY, Coquet JM, Berzins SP, Kyparissoudis K, Keating R, Pellicci DG, Hayakawa Y, Godfrey DI, Smyth MJ: Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med 2005;202:1279-1288.
  1330. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD: Cancer immunoediting: from immuno- surveillance to tumor escape. Nat Immunol 2002;3:991-998.
  1331. Schreiber H, Wu TH, Nachman J, Kast WM: Immunodominance and tumor escape. Semin Cancer Biol 2002;12:25-31.
  1332. Matsui S, Ahlers JD, Vortmeyer AO, Terabe M, Tsukui T, Carbone DP, Liotta LA, Berzofsky JA: A model for CD8ϩ CTL tumor immunosurveillance and regulation of tumor escape by CD4 T cells through an effect on quality of CTL. J Immunol 1999;163:184-193.
  1333. Dunn GP, Old LJ, Schreiber RD: The immunobiology of cancer immunosurveillance and immuno- editing. Immunity 2004;21:137-148.
  1334. Khong HT, Restifo NP: Natural selection of tumor variants in the generation of 'tumor escape' phenotypes. Nat Immunol 2002;3:999-1005.
  1335. O'Brien JM, Marcus DM, Bernards R, Carpenter JL, Windle JJ, Mellon PL, Albert DM: A trans- genic mouse model for trilateral retinoblastoma. Arch Ophthalmol 1990;108:1145-1151.
  1336. Morilla-Grasa A: Animal models in uveal melanoma: establishment and research. Can J Ophthalmol 2004;39:433-440.
  1337. Mo JS, Anderson MG, Gregory M, Smith RS, Savinova OV, Serreze DV, Ksander BR, Streilein JW, John SWM: By altering ocular immune privilege, bone marrow-derived cells pathogenically con- tribute to DBA/2J pigmentary glaucoma. J Exp Med 2003;197:1335-1344.
  1338. Apte RS, Sinha D, Mayhew E, Wistow GJ, Niederkorn JY: Cutting edge: role of macrophage migration inhibitory factor in inhibiting NK cell activity and preserving immune privilege. J Immunol 1998;160:5693-5696.
  1339. Taylor AW: The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (␣-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages. J Neuroimmunol 2005;162: 43-50.
  1340. Kezuka T, Streilein JW: Analysis of in vivo regulatory properties of T cells activated in vitro by TGF␤ 2 -treated antigen presenting cells. Invest Ophthalmol Vis Sci 2000;41:1410-1421.
  1341. Faunce DE, Stein-Streilein J: NKT cell-derived RANTES recruits APCs and CD8ϩ T cells to the spleen during the generation of regulatory T cells in tolerance. J Immunol 2002;169:31-38.
  1342. Skelsey ME, Mellon J, Niederkorn JY: ␥␦ T cells are needed for ocular immune privilege and corneal graft survival. J Immunol 2001;166:4327-4333.
  1343. Skelsey ME, Mayhew E, Niederkorn JY: CD25ϩ, interleukin-10-producing CD4ϩ T cells are required for suppressor cell production and immune privilege in the anterior chamber of the eye. Immunology 2003;110:18-29.
  1344. Kezuka T, Streilein JW: In vitro generation of regulatory CD8ϩ T cells similar to those found in mice with anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci 2000;41:1803-1811. References
  1345. Niederkorn JY: Immunology and immunomodulation of corneal transplantation. Int Rev Immunol 2002;21:173-196.
  1346. Aiken-O'Neill P , Mannis MJ: Summary of corneal transplant activity Eye Bank Association of America. Cornea 2002;21:1-3.
  1347. Zirm E: Eine erfolgreiche totale Keratoplastik. Graefes Arch Ophthalmol 1906;64:580-593.
  1348. Niederkorn JY: The immune privilege of corneal grafts. J Leukoc Biol 2003;74:167-171.
  1349. Auchincloss H Jr, Mayer T, Ghobrial R, Winn HJ: T -cell subsets, bm mutants, and the mechanisms of allogeneic skin graft rejection. Immunol Res 1989;8:149-164.
  1350. Sonoda Y , Streilein JW: Orthotopic corneal transplantation in mice -evidence that the immuno- genetic rules of rejection do not apply. Transplantation 1992;54:694-704.
  1351. Streilein JW: Immune regulation and the eye: a dangerous compromise. F ASEB J 1987;1:199-208.
  1352. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:879-889.
  1353. Niederkorn J: Immune privilege of the eye; in Chen LS (ed): Animal Models of Human Infla- mmatory Skin Diseases. New York, CRC Press, 2004, p 564.
  1354. Niederkorn JY: Immune privilege in the anterior chamber of the eye. Crit Rev Immunol 2002;22:13-46.
  1355. Barker CF, Billingham RE: Immunologically privileged sites. Adv Immunol 1977;25:1-54.
  1356. Medawar PB: Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol 1948;29:58-69.
  1357. Streilein JW, McCulley J, Niederkorn JY: Heterotopic corneal grafting in mice: a new approach to the study of corneal alloimmunity. Invest Ophthalmol Vis Sci 1982;23:489-500.
  1358. Streilein JW, Toews GB, Bergstresser PR: Corneal allografts fail to express Ia antigens. Nature 1979;282:326-327.
  1359. Wang HM, Kaplan HJ, Chan WC, Johnson M: The distribution and ontogeny of MHC antigens in murine ocular tissue. Invest Ophthalmol Vis Sci 1987;28:1383-1389.
  1360. Whitsett CF, Stulting RD: The distribution of HLA antigens on human corneal tissue. Invest Ophthalmol Vis Sci 1984;25:519-524.
  1361. Rubsamen PE, McCulley J, Bergstresser PR, Streilein JW: On the Ia immunogenicity of mouse corneal allografts infiltrated with Langerhans cells. Invest Ophthalmol Vis Sci 1984;25:513-518.
  1362. Tisher CC, Madsen KM: Anatomy of the kidney. Lymphatics; in Brenner BM (ed): Brenner's and Rector's The Kidney. Philadelphia, Saunders, 1996.
  1363. Dworkin LD, Brenner BM: The renal circulations; in Brenner BM (ed): Brenner's and Rector's The Kidney. Philadelphia, Saunders, 1996.
  1364. Foglia RP, DiPreta J, Statter MB, Donahoe PK: Fetal allograft survival in immunocompetent recip- ients is age dependent and organ specific. Ann Surg 1986;204:402-410.
  1365. McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL: The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science 1988;241:1632-1639.
  1366. Reece-Smith H, Du Toit DF, McShane P, Morris PJ: Prolonged survival of pancreatic islet allo- grafts transplanted beneath the renal capsule. Transplantation 1981;31:305-306.
  1367. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC: A role for CD95 ligand in pre- venting graft rejection. Nature 1995;377:630-632.
  1368. Hori J, Joyce N, Streilein JW: Epithelium-deficient corneal allografts display immune privilege beneath the kidney capsule. Invest Ophthalmol Vis Sci 2000;41:443-452.
  1369. Hori J, Joyce NC, Streilein JW: Immune privilege and immunogenicity reside among different lay- ers of the mouse cornea. Invest Ophthalmol Vis Sci 2000;41:3032-3042.
  1370. Khodadoust AA, Silverstein AM: Transplantation and rejection of individual cell layers of the cornea. Invest Ophthalmol 1969;8:180-195.
  1371. Stuart PM, Griffith TS, Usui N, Pepose J, Yu X, Ferguson TA: CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival. J Clin Invest 1997;99:396-402.
  1372. Yamagami S, Kawashima H, Tsuru T, Yamagami H, Kayagaki N, Yagita H, Okumura K, Gregerson DS: Role of Fas-Fas ligand interactions in the immunorejection of allogeneic mouse corneal trans- plants. Transplantation 1997;64:1107-1111.
  1373. Sano Y, Ksander BR, Streilein JW: Fate of orthotopic corneal allografts in eyes that cannot support anterior chamber-associated immune deviation induction. Invest Ophthalmol Vis Sci 1995;36: 2176-2185.
  1374. Sano Y, Okamoto S, Streilein JW: Induction of donor-specific ACAID can prolong orthotopic corneal allograft survival in 'high-risk' eyes. Curr Eye Res 1997;16:1171-1174.
  1375. Sonoda Y, Sano Y, Ksander B, Streilein JW: Characterization of cell-mediated immune responses elicited by orthotopic corneal allografts in mice. Invest Ophthalmol Vis Sci 1995;36:427-434.
  1376. Sonoda A, Sonoda Y, Muramatu R, Streilein JW, Usui M: ACAID induced by allogeneic corneal tissue promotes subsequent survival of orthotopic corneal grafts. Invest Ophthalmol Vis Sci 2000;41:790-798.
  1377. Yamada J, Streilein JW: Induction of anterior chamber-associated immune deviation by corneal allografts placed in the anterior chamber. Invest Ophthalmol Vis Sci 1997;38:2833-2843.
  1378. Treseler PA, Foulks GN, Sanfilippo F: The relative immunogenicity of corneal epithelium, stroma, and endothelium. The role of major histocompatibility complex antigens. Transplantation 1986;41: 229-234.
  1379. Tuberville AW, Foster CS, Wood TO: The effect of donor cornea epithelium removal on the inci- dence of allograft rejection reactions. Ophthalmology 1983;90:1351-1356.
  1380. Hori J, Streilein JW: Role of recipient epithelium in promoting survival of orthotopic corneal allo- grafts in mice. Invest Ophthalmol Vis Sci 2001;42:720-726.
  1381. She SC, Steahly LP, Moticka EJ: A method for performing full-thickness, orthotopic, penetrating keratoplasty in the mouse. Ophthalmic Surg 1990;21:781-785.
  1382. Williams KA, Coster DJ: Penetrating corneal transplantation in the inbred rat: a new model. Invest Ophthalmol Vis Sci 1985;26:23-30.
  1383. Sano Y, Ksander BR, Streilein JW: Murine orthotopic corneal transplantation in high-risk eyes. Rejection is dictated primarily by weak rather than strong alloantigens. Invest Ophthalmol Vis Sci 1997;38:1130-1138.
  1384. Maguire MG, Stark WJ, Gottsch JD, Stulting RD, Sugar A, Fink NE, Schwartz A: Risk factors for corneal graft failure and rejection in the Collaborative Corneal Transplantation Studies. Collaborative Corneal Transplantation Studies Research Group. Ophthalmology 1994;101: 1536-1547.
  1385. The Collaborative Corneal Transplantation Studies Research Group: Effectiveness of histocom- patibility matching in high-risk corneal transplantation. Arch Ophthalmol 1992;110:1392-1403.
  1386. Volker-Dieben HJ, Kok-van Alphen CC, Lansbergen Q, Persijn GG: Different influences on corneal graft survival in 539 transplants. Acta Ophthalmol (Copenh) 1982;60:190-202.
  1387. Hori J, Streilein JW: Survival in high-risk eyes of epithelium-deprived orthotopic corneal allografts reconstituted in vitro with syngeneic epithelium. Invest Ophthalmol Vis Sci 2003;44:658-664.
  1388. Niederkorn JY: The immune privilege of corneal allografts. Transplantation 1999;67:1503-1508.
  1389. McKinney EC, Streilein JW: On the extraordinary capacity of allogeneic epidermal Langerhans cells to prime cytotoxic T cells in vivo. J Immunol 1989;143:1560-1564.
  1390. Callanan D, Peeler J, Niederkorn JY: Characteristics of rejection of orthotopic corneal allografts in the rat. Transplantation 1988;45:437-443.
  1391. He YG, Niederkorn JY: Depletion of donor-derived Langerhans cells promotes corneal allograft survival. Cornea 1996;15:82-89.
  1392. Sonoda Y, Streilein JW: Impaired cell-mediated immunity in mice bearing healthy orthotopic corneal allografts. J Immunol 1993;150:1727-1734.
  1393. Skelsey ME, Mellon J, Niederkorn JY: ␥␦ T cells are needed for ocular immune privilege and corneal graft survival. J Immunol 2001;166:4327-4333.
  1394. Niederkorn JY, Mellon J: Anterior chamber-associated immune deviation promotes corneal allo- graft survival. Invest Ophthalmol Vis Sci 1996;37:2700-2707.
  1395. She SC, Steahly LP, Moticka EJ: Intracameral injection of allogeneic lymphocytes enhances corneal graft survival. Invest Ophthalmol Vis Sci 1990;31:1950-1956.
  1396. Niederkorn JY: The immunology of corneal transplantation. Dev Ophthalmol 1999;30:129-140.
  1397. Hegde S, Mellon JK, Hargrave SL, Niederkorn JY: Effect of alloantibodies on corneal allograft survival. Invest Ophthalmol Vis Sci 2002;43:1012-1018.
  1398. Bora NS, Gobleman CL, Atkinson JP, Pepose JS, Kaplan HJ: Differential expression of the com- plement regulatory proteins in the human eye. Invest Ophthalmol Vis Sci 1993;34:3579-3584.
  1399. Lass JH, Walter EI, Burris TE, Grossniklaus HE, Roat MI, Skelnik DL, Needham L, Singer M, Medof ME: Expression of two molecular forms of the complement decay-accelerating factor in the eye and lacrimal gland. Invest Ophthalmol Vis Sci 1990;31:1136-1148.
  1400. Dr. Junko Hori Department of Ophthalmology Nippon Medical School 1-5-1, Sendagi, Bunkyo, Tokyo, 113-8602 (Japan)
  1401. Tel. ϩ81 3 3822 2131, Fax ϩ81 3 5685 0988, E-Mail jhori-tky@umin.ac.jp References
  1402. Wenkel H, Streilein JW , Y oung MJ: Systemic immune deviation in the brain that does not depend on the integrity of the blood-brain barrier. J Immunol 2000;164:5125-5131.
  1403. Jiang LQ, Jorquera M, Streilein JW: Subretinal space and vitreous cavity as immunologically priv- ileged sites for retinal allografts. Invest Ophthalmol Vis Sci 1993;34:3347-3354.
  1404. Wenkel H, Chen PW , Ksander BR, Streilein JW: Immune privilege is extended, then withdrawn, from allogeneic tumor cell grafts placed in the subretinal space. Invest Ophthalmol Vis Sci 1999;40:3202-3208.
  1405. Jiang LQ, Streilein JW: Immunity and immune privilege elicited by autoantigens expressed on syngeneic neonatal neural retina grafts. Curr Eye Res 1992;11:697-709.
  1406. Jiang LQ, Streilein JW: Immune responses elicited by transplantation and tissue-restricted anti- gens expressed on retinal tissues implanted subconjunctivally. Transplantation 1991;52:513-519.
  1407. Jiang LQ, Jorquera M, Streilein JW: Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts. Exp Eye Res 1994;58:719-728.
  1408. Wenkel H, Streilein JW: Analysis of immune deviation elicited by antigens injected into the sub- retinal space. Invest Ophthalmol Vis Sci 1998;39:1823-1834.
  1409. Gregerson DS, Dou C: Spontaneous induction of immunoregulation by an endogenous retinal antigen. Invest Ophthalmol Vis Sci 2002;43:2984-2991.
  1410. Ng TF , Streilein JW: Light-induced migration of retinal microglia into the subretinal space. Invest Ophthalmol Vis Sci 2001;42:3301-3310.
  1411. Ng TF, Cho KS, Osawa H, Streilein JW: Bright light, by recruiting microglia to the subretinal space prejudices survival of neonatal neuronal retina allografts (abstract). Invest Ophthalmol Vis Sci 2002;43:2291.
  1412. Ma N, Streilein JW: T cell immunity induced by allogeneic microglia in relation to neuronal retina transplantation. J Immunol 1999;162:4482-4489.
  1413. Gregerson DS, Yang J: CD45-positive cells of the retina and their responsiveness to in vivo and in vitro treatment with IFN-gamma or anti-CD40. Invest Ophthalmol Vis Sci 2003;44:3083-3093.
  1414. Hori J, Joyce N, Streilein JW: Epithelium-deficient corneal allografts display immune privilege beneath the kidney capsule. Invest Ophthalmol Vis Sci 2000;41:443-452.
  1415. Reece-Smith H, Du Toit DF, McShane P, Morris PJ: Prolonged survival of pancreatic islet allo- grafts transplanted beneath the renal capsule. Transplantation 1981;31:305-306.
  1416. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC: A role for CD95 ligand in pre- venting graft rejection. Nature 1995;377:630-632.
  1417. Takahashi M, Palmer TD, Takahashi J, Gage FH: Widespread integration and survival of adult- derived neural progenitor cells in the developing optic retina. Mol Cell Neurosci 1998;12: 340-348.
  1418. Young MJ, Ray SJO, Whiteley SJO, Klassen HJ, Gage FH: Integration of transplanted neural prog- enitor cells into the retina of immature and mature dystrophic rats. Mol Cell Neurosci 2000;16: 197-205. Farrokh-Siar L, Rezai KA, Semnani RT, Patel SC, Ernest JT, Peterson EJ, Koretzky GA, van Seventer GA: Human fetal retinal pigment epithelial cells induce apoptosis in the T-cell line Jurkat. Invest Ophthalmol Vis Sci 1999;40:1503-1511.
  1419. Kaestel CG, Lovato P, Odum N, Nissen MH, Ropke C: The immune privilege of the eye: human retinal pigment epithelial cells selectively modulate T-cell activation in vitro. Curr Eye Res 2005;30:375-383.
  1420. Sun D, Enzmann V, Lei S, Sun SL, Kaplan HJ, Shao H: Retinal pigment epithelial cells activate uveitogenic T cells when they express high levels of MHC class II molecules, but inhibit T cell activation when they express restricted levels. J Neuroimmunol 2003;144:1-8.
  1421. Willermain F, Caspers-Velu L, Nowak B, Stordeur P, Mosselmans R, Salmon I, Velu T, Bruyns C: Retinal pigment epithelial cells phagocytosis of T lymphocytes: possible implication in the immune privilege of the eye. Br J Ophthalmol 2002;86:1417-1421.
  1422. Wenkel H, Streilein JW: Evidence that retinal pigment epithelium functions as an immune- privileged tissue. Invest Ophthalmol Vis Sci 2000;41:3467-3473.
  1423. Ng TF, Osawa H, Hori J, Young MJ, Streilein JW: Allogeneic neonatal neuronal retina grafts display partial immune privilege in the subcapsular space of the kidney. J Immunol 2002;169: 5601-5606.
  1424. Ma N, Streilein JW: Contribution of microglia as passenger leukocytes to the fate of intraocular neuronal retinal grafts. Invest Ophthalmol Vis Sci 1998;39:2384-2393.
  1425. Gage FH, Ray J, Fisher LJ: Isolation, characterization, and use of stem cells from the CNS. Annu Rev Neurosci 1995;18:159-192.
  1426. Yandava BD, Billinghurst LL, Snyder EY: 'Global' cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. Proc Natl Acad Sci USA 1999;96:7029-7034.
  1427. Huh GS, Boulanger LM, Du H, Riquelme PA, Brotz TM, Shatz CJ: Functional requirement for class I MHC in CNS development and plasticity. Science 2000;290:2155-2159.
  1428. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-1147.
  1429. Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD: Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA 1998;95:13726-13731.
  1430. Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL: Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 1999;283:534-537.
  1431. Clarke DL, Johansson CB, Wilbertz J, Veress B, Nilsson E, Karlstrom H, Lendahl U, Frisen J: Generalized potential of adult neural stem cells. Science 2000;288:1660-1663.
  1432. Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M: Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000;6:1229-1234.
  1433. Madrazo I, Leon V, Torres C, Aguilera MC, Varela G, Alvarez F, Fraga A, Drucker-Colin R, Ostrosky F, Skurovich M, Franco R: Transplantation of fetal substantia nigra and adrenal medulla to the caudate nucleus in two patients with Parkinson's disease. N Engl J Med 1988;318:51.
  1434. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S: Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 2001;344:710-719.
  1435. Hagell P, Schrag A, Piccini P, Jahanshahi M, Brown R, Rehncrona S, Widner H, Brundin P, Rothwell JC, Odin P, Wenning GK, Morrish P, Gustavii B, Bjorklund A, Brooks DJ, Marsden CD, Quinn NP, Lindvall O: Sequential bilateral transplantation in Parkinson's disease: effects of the second graft. Brain 1999;122:1121-1132.
  1436. Klassen H, Imfeld KL, Ray J, Young MJ, Gage FH, Berman MA: The immunological properties of adult hippocampal progenitor cells. Vision Res 2003;43:947-956.
  1437. Hori J, Ng TF, Shatos M, Klassen H, Streilein JW, Young MJ: Neural progenitor cells lack immunogenicity and resist destruction as allografts. Stem Cells 2003;21:405-416.
  1438. Klassen H, Schwartz MR, Bailey AH, Young MJ: Surface markers expressed by multipotent human and mouse neural progenitor cells include tetraspanins and non-protein epitopes. Neurosci Lett 2001;312:180-182.
  1439. Schwartz PH, Bryant PJ, Fuja TJ, Su H, O'Dowd DK, Klassen H: Isolation and characterization of neural progenitor cells from post-mortem human cortex. J Neurosci Res 2003;74:838-851.
  1440. Klassen H, Ziaeian B, Kirov II, Young MJ, Schwartz PH: Isolation of retinal progenitor cells from post-mortem human tissue and comparison with autologous brain progenitors. J Neurosci Res 2004;77:334-343.
  1441. Ahmad I, Dooley CM, Thoreson WB, Rogers JA, Afiat S: In vitro analysis of a mammalian retinal progenitor that gives rise to neurons and glia. Brain Res 1999;831:1-10.
  1442. Yang P, Seiler MJ, Aramant RB, Whittemore SR: Differential lineage restriction of rat retinal prog- enitor cells in vitro and in vivo. J Neurosci Res 2002;69:466-476.
  1443. Schwartz PH, Nethercott H, Kirov II, Ziaeian B, Young MJ, Klassen H: Expression of neurodevel- opmental markers by cultured porcine neural precursor cells. Stem Cells 2005;23:1286-1294. Dr. Michael J. Young Schepens Eye Research Institute Harvard Medical School, 20 Staniford Street Boston, MA 02114 (USA) Tel. ϩ1 617 912 7419, Fax ϩ1 617 912 0101, E-Mail mikey@vision.eri.harvard.edu
  1444. Niederkorn JY, Kaplan HJ (eds): Immune Response and the Eye. Chem Immunol Allergy. Basel, Karger, 2007, vol 92, pp 317-327 Therapies Based on Principles of Ocular Immune Privilege Jie Zhang-Hoover, Joan Stein-Streilein Schepens Eye Research Institute, and Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., USA References
  1445. Kaplan HJ, Streilein JW: Do immunologically privileged sites require a functioning spleen? Nature 1974;251:553-554.
  1446. Kaplan HJ, Streilein JW , Stevens TR: Transplantation immunology of the anterior chamber of the eye. II. Immune response to allogeneic cells. J Immunol 1975;118:809-814.
  1447. Kaplan HJ, Streilein JW: Immune response to immunization via the anterior chamber of the eye. I. F1-lymphocyte-induced immune deviation. J Immunol 1977;118:809-814.
  1448. Kaplan HJ, Streilein JW: Immune response to immunization via the anterior chamber of the eye. II. An analysis of F1 lymphocyte-induced immune deviation. J Immunol 1978;120:689-693.
  1449. Niederkorn J, Streilein JW , Shadduck JA: Deviant immune responses to allogeneic tumors injected intracamerally and subcutaneously in mice. Invest Ophthalmol Vis Sci 1980;20:355-363.
  1450. Streilein JW , Niederkorn JY: Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J Exp Med 1981;153:1058-1067.
  1451. Niederkorn JY , Streilein JW: Alloantigens placed into the anterior chamber of the eye induce spe- cific suppression of delayed type hypersensitivity but normal cytotoxic T lymphocyte responses. J Immunol 1983;131:2670-2674.
  1452. Streilein JW , Niederkorn JY: Characterization of the suppressor cell(s) responsible for anterior chamber-associated immune deviation (ACAID) induced in BALB/c mice by P815 cells. J Immunol 1985;134:1381-1387.
  1453. Niederkorn JY , Mellon J: Anterior chamber-associated immune deviation promotes corneal allo- graft survival. Invest Ophthalmol Vis Sci 1996;37:2700-2707.
  1454. Sonoda A, Sonoda Y, Muramatu R, Streilein JW, Usui M: ACAID induced by allogeneic corneal tissue promotes subsequent survival of orthotopic corneal grafts. Invest Ophthalmol Vis Sci 2000;41:790-798.
  1455. Sonoda Y, Streilein JW: Impaired cell-mediated immunity in mice bearing healthy orthotopic corneal allografts. Immunology 1993;150:1727-1734.
  1456. Sonoda Y, Sano Y, Ksander B, Streilein JW: Characterization of cell-mediated immune responses elicited by orthotopic corneal allografts in mice. Invest Ophthalmol Vis Sci 1995;36:427-434.
  1457. Streilein JW: Immunobiology and immunopathology of corneal transplantation; in Streilein JW (ed): Immune Response and the Eye. Chem Immunol. Basel, Karger, 1999, vol 73, pp 186-206.
  1458. Hara Y, Caspi RR, Wiggert B, Chan CC, Wilbanks GA, Streilein JW: Suppression of experimental autoimmune uveitis in mice by induction of anterior chamber-associated immune deviation with interphotoreceptor retinoid-binding protein. J Immunol 1992;148:1685-1692.
  1459. Mizuno K, Altman NF, Clark AF, Streilein JW: Histopathologic analysis of experimental autoim- mune uveitis attenuated by intracameral injection of S-antigen. Curr Eye Res 1989;8:113-121.
  1460. Hara Y, Caspi RR, Wiggert B, Dorf M, Streilein JW: Analysis of an in vitro-generated signal that induces systemic immune deviation similar to that elicited by antigen injected into the anterior chamber of the eye. J Immunol 1992;149:1531-1538.
  1461. Cousins SW, McCabe MM, Danielpour D, Streilein JW: Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 1991;32:2201-2211.
  1462. Hara Y, Okamoto S, Rouse B, Streilein JW: Evidence that peritoneal exudate cells cultured with eye-derived fluids are the proximate antigen-presenting cells in immune deviation of the ocular type. J Immunol 1993;151:5162-5171.
  1463. Kezuka T, Streilein JW: In vitro generation of regulatory CD8 ϩ T cells similar to those found in mice with anterior chamber associated immune deviation. Invest Ophthalmol Vis Sci 2000;41: 1803-1811.
  1464. Kezuka T, Streilein JW: Analysis of in vivo regulatory properties of T cells activated in vitro by TGF␤2-treated antigen presenting cells. Invest Ophthalmol Vis Sci 2000;41:1410-1421.
  1465. Wilbanks GA, Mammolenti M, Streilein JW: Studies on the induction of anterior chamber-associated immune deviation (ACAID). III. Induction of ACAID depends upon intraocular transforming growth factor-beta. Eur J Immunol 1992;22:165-173.
  1466. Wilbanks GA, Mammolenti M, Streilein JW: Studies on the induction of anterior chamber-associated immune deviation (ACAID). II. Eye-derived cells participate in generating blood-borne signals that induce ACAID. J Immunol 1991;146:3018-3024.
  1467. Wilbanks GA, Streilein JW: Studies on the induction of anterior chamber-associated immune deviation (ACAID). I. Evidence that an antigen-specific, ACAID-inducing, cell-associated signal exists in the peripheral blood. J Immunol 1991;146:2610-2617.
  1468. Wilbanks GA, Streilein JW: Fluids from immune privileged sites endow macrophages with the capacity to induce antigen-specific immune deviation via a mechanism involving transforming growth factor-beta. Eur J Immunol 1992;22:1031-1036.
  1469. Wilbanks GA, Streilein JW: Characterization of suppressor cells in anterior chamber-associated immune deviation (ACAID) induced by soluble antigen. Evidence of two functionally and pheno- typically distinct T-suppressor cell populations. Immunology 1990;71:383-389.
  1470. Kosiewicz MM, Okamoto S, Miki S, Ksander BR, Shimizu T, Streilein JW: Imposing deviant immunity on the presensitized state. J Immunol 1994;153:2962-2973.
  1471. Wilbanks GA, Streilein JW: Macrophages capable of inducing anterior chamber associated immune deviation demonstrate spleen-seeking migratory properties. Reg Immunol 1992;4: 130-137.
  1472. Niederkorn JY, Mayhew E: Role of splenic B cells in the immune privilege of the anterior cham- ber of the eye. Eur J Immunol 1995;25:2783-2787.
  1473. Faunce DE, Sonoda KH, Stein-Streilein J: MIP-2 recruits NKT cells to the spleen during tolerance induction. J Immunol 2001;166:313-321.
  1474. D'Orazio TJ, Niederkorn JY: Splenic B cells are required for tolerogenic antigen presentation in the induction of anterior chamber-associated immune deviation (ACAID). Immunology 1998;95:47-55.
  1475. Skelsey ME, Mayhew E, Niederkorn JY: Splenic B cells act as antigen presenting cells for the induction of anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci 2003;44: 5242-5251.
  1476. D'Orazio TJ, Mayhew E, Niederkorn JY: Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1. J Immunol 2001;166:26-32.
  1477. Sonoda KH, Stein-Streilein J: CD1d on antigen-transporting APC and splenic marginal zone B cells promotes NKT cell-dependent tolerance. Eur J Immunol 2002;32:848-857.
  1478. Lutz MB, Schuler G: Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 2002;23:445-449.
  1479. Rutella S, Lemoli RM: Regulatory T cells and tolerogenic dendritic cells: from basic biology to clinical applications. Immunol Lett 2004;94:11-26.
  1480. Bilsborough J, George TC, Norment A, Viney JL: Mucosal CD8␣ϩ DC, with a plasmacytoid phe- notype, induce differentiation and support function of T cells with regulatory properties. Immunology 2003;108:481-492.
  1481. Akbari O, DeKruyff R, Umetsu D: Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2001;2:725-731.
  1482. Dhodapkar M, Steinman R, Krasovsky J, Munz C, Bhardwaj N: Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001;193:233-238.
  1483. Groux H, Fournier N, Cottrez F: Role of dendritic cells in the generation of regulatory T cells. Semin Immunol 2004;16:99-106.
  1484. Adorini L, Giarratana N, Penna G: Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol 2004;16:127-134.
  1485. Kuchroo VK, Minami M, Diamond B, Dorf ME: Functional analysis of cloned macrophage hybrido- mas. VI. Differential ability to induce immunity or suppression. J Immunol 1988;141: 10-16.
  1486. Masli S, Turpie B, Hecker KH, Streilein JW: Expression of thrombospondin in TGFß-treated APCs and its relevance to their immune deviation-promoting properties. J Immunol 2002;168: 2264-2273.
  1487. Zhang-Hoover J, Stein-Streilein J: Tolerogenic APC generate CD8ϩ T regulatory cells that modu- late pulmonary interstitial fibrosis. J Immunol 2004;172:178-185.
  1488. Katagiri K, Zhang-Hoover J, Mo JS, Stein-Streilein J, Streilein JW: Using tolerance induced via the anterior chamber of the eye to inhibit Th2-dependent pulmonary pathology. J Immunol 2002;169:84-89.
  1489. Zhang-Hoover J, Finn P, Stein-Streilein J: Modulation of ovalbumin-induced airway inflammation and hyperactivity by tolerogenic APC. J Immunol 2005;175:7117-7124.
  1490. Kosiewicz MM, Alard P, Liang S, Clark SL: Mechanisms of tolerance induced by transforming growth factor-beta-treated antigen-presenting cells: CD8 regulatory T cells inhibit the effector phase of the immune response in primed mice through a mechanism involving Fas ligand. Int Immunol 2004;16:697-706.
  1491. Keino H, Masli S, Sasaki S, Streilen JW, Stein-Streilein J: CD8ϩ T regulatory cells use a novel genetic program that includes CD103 to suppress Th1 immunity in eye-derived tolerance. Invest Ophthalmol Vis Sci 2006;47:1533-1542.
  1492. Gordon JR, Li F, Nayyar A, Xiang J, Zhang X: CD8␣ϩ, but not CD8␣Ϫ, dendritic cells tolerize Th2 responses via contact-dependent and -independent mechanisms, and reverse airway hyperre- sponsiveness, Th2, and eosinophil responses in a mouse model of asthma. J Immunol 2005;175: 1516-1522.
  1493. Okamoto S, Kosiewicz MM, Caspi RR, Streilein JW: ACAID as a potential therapy for established experimental autoimmune uveitis; in Nussenblatt RB, Whitcup SM, Caspi RR, Gery I (eds): Advances in Ocular Immunology Amsterdam, Elsevier, 1994, pp 195-198.
  1494. Streilein JW: Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 2003;74:179-185.
  1495. Faunce DE, Terajewicz A, Stein-Streilein J: Cutting edge: in vitro-generated tolerogenic APC induce CD8ϩ T regulatory cells that can suppress ongoing experimental autoimmune encephalomyelitis. J Immunol 2004;172:1991-1995.
  1496. Nakamura T, Terajewicz A, Stein-Streilein J: Mechanisms of peripheral tolerance following intra- cameral inoculation are independent of IL-13 or STAT6. J Immunol 2005;175:2643-2646.
  1497. Kosiewicz MM, Streilein JW: Is deviant immunity induced by intraocular injection of antigen dependent on Th2 cells? Invest Ophthalmol Vis Sci 1996;37:S1136.
  1498. Streilein JW: Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat Rev Immunol 2003;3:878-889.
  1499. Kezuka T, Sakai JI, Usui N, Streilein JW, Usui M: Evidence for antigen-specific immune deviation in patients with acute retinal necrosis. Arch Ophthalmol 2001;119:1044-1049.
  1500. Dr. Jie Zhang-Hoover Schepens Eye Research Institute 20 Staniford Street Boston, MA 02114 (USA)
  1501. Tel. ϩ1 617 912 7493, Fax ϩ1 617 912 0105, E-Mail jzhoover@vision.eri.harvard.edu Atherton, S.S. 244
  1502. Barabino, S. 176
  1503. Bora, N.S. 105, 213
  1504. Bora, P.S. 105
  1505. Callegan, M.C. 266
  1506. Chen, P.W. 276
  1507. Cursiefen, C. 50
  1508. Dana, M.R. 58, 176, 195
  1509. Ferguson, T.A. 140
  1510. Flynn, T.H. 166
  1511. Forrester, J.V. 228
  1512. Frank, G.M. 203
  1513. Gillette-Ferguson, I. 254
  1514. Gilmore, M.S. 266
  1515. Gregory, M. 266
  1516. Griffith, T.S. 140
  1517. Hamrah, P. 58
  1518. Hazlett, L.D. 185
  1519. Hendricks, R.L. 203
  1520. Hori, J. 290, 300
  1521. Jha, P. 105
  1522. Kaplan, H.J. 1, 4, 11, 94, 105, 155, 213
  1523. Kezuka, T. 244
  1524. Klassen, H.J. 300
  1525. Knop, E. 36
  1526. Knop, N. 36
  1527. Ksander, B.R. 276
  1528. Lepisto, A.J. 203
  1529. Manzouri, B. 166
  1530. Mo, J.-S. 155
  1531. Ng, T.F. 300
  1532. Niederkorn, J.Y. 1, 11, 27, 131, 290
  1533. Ono, S.J. 166 Pearlman, E. Rashid, S. 195
  1534. Shao, H. 94
  1535. Siddique, M. Sohn, J.-H. 105
  1536. Stein-Streilein, J. 115, 317
  1537. Streilein, J.W. Sugita, S. 86
  1538. Sun, D. 94
  1539. Taylor, A.W. 71
  1540. Tezel, G. 221
  1541. Tezel, T.H. 105
  1542. Wang, W. 155
  1543. Watte, C. 115
  1544. Wax, M.B. 221
  1545. Young, M.J. 300
  1546. Zamiri, P. 86
  1547. Zhang-Hoover, J. 317