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N. Kitaichi, A.W. Taylor; The Regulatory Cells That Emerge in Autoimmune Uveitis Prevent Memory Immunity to Retinal Autoantigens . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1051.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have demonstrated that regulatory T cells (Treg cells) emerge in the spleens of mice that have recovered from experimental autoimmune uveoretinitis (EAU). Their presence in the spleen is dependent on an intact eye and the expression of melanocortin 5 receptor (MC5r). We examined the possibility that such Treg cells are involved in the resistance of mice to a reoccurrence of EAU. Methods: EAU was induced by immunizing C57BL/6, MC5r knockout (MC5r-/-), and B10.RIII mice with specific immunodominant peptides of human interphotoreceptor retinoid-binding protein (IRBPp) with complete Freund's adjuvant (CFA). After the uveitis resolved, C57BL/6 and MC5r-/- mice were reimmunized with IRBPp emulsified in synthetic adjuvant . For adoptive transfer experiments, T cells from spleens of mice that have recovered from uveitis were activated in vitro with antigen-pulsed antigen presenting cells. The T cells from the cultures were enriched for CD4(+) T cells, and adoptively transferred into syngeneic EAU-susceptible mice. The course and severity of EAU was observed and scored. Adoptive transfer of T cells into EAU-susceptible B10.RIII mice were depleted of CD25(+) T cells with antibody coated magnetic beads before the adoptive transfer. Results: Following reimmunization the MC5r-/- mice expressed an accelerated onset and severe uveitis compared to the delayed and mild uveitis of reimmunized wild type mice. Moreover, the adoptive transfer of CD4(+) T cells from wild type mice that recovered from EAU suppressed the severity of EAU in the MC5r-/- mice. The Treg cells in the spleens of wild type mice that have recovered from EAU are CD4(+) CD25(+) T cells and are present only after the uveitis begins to show clinical signs of resolving. Conclusions: Mice recovering from EAU express Treg cells whose presence prevents development of a memory immune response to retinal autoantigen. Our results suggest that the reestablishment of the ocular immunosuppressive microenvironment to resolve autoimmune uveitis mediates induction of regulatory T cells specific to retinal autoantigens.
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