Experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are CD4+ T cell-mediated inflammatory diseases of the uveal tract and retina of the eye and of the pineal gland. EAU and EAP can be induced by several retinal autoantigens including S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP). In this study we investigated the effect of intravenous administration of S-Ag and IRBP coupled to syngeneic spleen cells on the development of EAU and EAP. Injection of S-Ag or IRBP coupled to spleen cells 5 days prior to immunization with native S-Ag or IRBP, respectively, was effective in preventing the induction of EAU and EAP in LEW rats. Conversely, LEW rats receiving S-Ag-coupled spleen cells and challenged with IRBP or LEW rats receiving IRBP-coupled spleen cells and challenged with S-Ag developed a severe EAU within 10 days to 2 weeks following immunization, as did all control animals receiving sham-coupled spleen cells and challenged with the two retinal antigens. The results show that the administration of retinal autoantigens coupled to spleen cells effectively protects against the development of EAU when animals are subsequently challenged with the tolerizing antigen but not when challenged with another unrelated pathogenic retinal autoantigen.
Bibliographical noteFunding Information:
’ Supported in part by the Retina Service, Wills Eye Hospital, National Institutes of Health Grants EYS095 and BRSG55 10, the Pennsylvania Lions Sight Conservation and Eye Research Foundation, Research to Prevent Blindness, Inc., the Crippled Childrens Vitreo-Retinal Research Foundation (David Meyer, M.D., Director), the Elizabeth C. Ring Trust, and the Grampian Health Board, Aberdeen, Scotland (H. S. Dua). H. S. Dua, M.D., Ph.D., is the Henry and Corinne Bower Retina Research Scholar. Larry A. Donoso, M.D., Ph.D., is the Thomas D. Duane Professor of Ophthalmology. Dale S. Gregerson is an RPB Senior Scientific Investigator. * To whom reprint requests should be addressed at Wills Eye Hospital, 9th and Walnut Streets, Philadelphia, PA 19107. 3 Abbreviations used: CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; EAP, experimental autoimmune pinealitis; EAU, experimental autoimmune uveitis; ECDI, l-ethyl-3-(3-dimethylaminopropyl) carbodiimide; IRBP, interphotoreceptor retinoid binding protein; LEW, Lewis; MBP, myelin basic protein; MSCH, mouse spinal chord homogenate; S-Ag, S-antigen; SCS, spleen cell suspension.