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RR Caspi, D Avichezer, C-C Chan, GM Lewis, B Wiggert, G Liou; Immunologically Privileged Expression of the Retinal Self-antigen IRBP Results in Tolerance . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1953.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Experimental autoimmune uveitis (EAU) can be induced by immunization with IRBP, an immunologically privileged antigen expressed in the retina. It has been argued that EAU-susceptible mice are not tolerant to IRBP due to: 1) its lack of detectable expression in the thymus by RT-PCR and Western blotting, which limits induction of central tolerance and 2) its relatively sequestered nature, which limits induction of peripheral tolerance. Here, we address this issue directly by analyzing the consequences of genetic IRBP deficiency vs. sufficiency on responses to this antigen. Methods: IRBP-knockout (KO) and wild type (WT) mice on the highly EAU-susceptible B10.RIII background were challenged with a uveitogenic regimen of IRBP and were evaluated for EAU scores, IRBP-specific cellular responses, and ability of their primed T cells to transfer disease. Results: IRBP KO mice lacked IRBP immunoreactivity in the retina and did not develop EAU, confirming lack of a target molecule. The KO mice showed strongly enhanced in vivo and in vitro cellular responses to IRBP, and their primed lymphoid cells induced more severe EAU upon adoptive transfer to naïve WT recipients than did WT cells. Sensitive immunohistochemical staining for IRBP revealed sparse positively staining cells in the WT, but not the KO thymus. Conclusion: IRBP-susceptible WT mice expressing endogenous IRBP in an immunologically privileged fashion nevertheless display a measurable and functionally significant tolerance to this antigen. This tolerance may in part be related to centrally acting mechanisms.
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