Analysis of T cell Tolerance induction against the retinal self- antigen IRBP

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Interphotoreceptor retinoid-binding protein (IRBP), which localizes specifically in the retina and the pineal gland, has been found to be highly immunopathogenic and capable of inducing experimental autoimmune uveoretinitis in a variety of animal species. However, since self-antigens such as IRBP normally exist in the body without causing uveoretinitis, it follows that self tolerance usually develops is still poorly understood. Nevertheless, recent work has provided direct evidence that T cell tolerance can occur by at least two different mechanisms involving interaction with self-antigens : clonal deletion in the thymus, and anergy in the periphery. In this study, we investigated whether endogenous IRBP also influences the induction of T cell tolerance against it. To that end, we removed the eyes and pineal glands of nude mice to eliminate endogenous IRBP,and reconstituted their T cell function by embryonic syngenic mouse thymus grafting (OxPxTg nude mice). Then, when we examined the lymphocyte response of the OxPxTg mice stimulated with IRBP,the significant proliferative response and production of IL-2 were observed, but not to be shown in that of normal BALB/c mice. Moreover, an IRBP specific T cell line established from the OxPxTg nude mice transferred into intact BALB/c nude mice was capable of inducing uveoretinitis. As a result of these findings, we elucidated that the organ-specific self-antigen IRBP is not merely the target antigen of the autoimmune disease known as uveoretinitis, but in the normal state it is also involved in the acquisition of T cell tolerance to itself (IRBP).