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SW McPherson; Analysis of CD8+ T Cell Recognition of a Retinal Self-Antigen . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2294.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Consistent with our hypothesis that an important mechanism of retinal immune privilege is antigen sequestration, we have previously demonstrated resting, CD44hi CD4+ T cells specific for an immunodominant epitope of beta-galactosidase (b-gal) give no evidence of recognition of their target antigen if it is expressed in the retina. In this study, we ask if CD8+ T cells are similarly inhibited in their recognition of b-gal expressed in the retina. Methods: Resting CD8+ T cells specific for an H-2 Ld-restricted immunodominant epitope of b-gal were labeled with CFSE and inoculated into normal and transgenic (Tg) mice which express b-gal in the retina only (hi-arr-b-gal), or in the brain and eye (GFAP), or widely (ROSA26) in the body. Spleens were recovered and examined by flow cytometry for CFSE-positive T cells. Activated CD8+ T cells were also transferred to determine if they would mediate autoimmune disease in the retina, which would demonstrate local recognition of the antigen by the CD8+ T cells. Results: b-gal specific CD8+ T cells recovered from mice expressing b-gal in the retina showed little reduction in number and CFSE staining intensity compared to those recovered from b-gal negative controls, indicating minimal, if any, recognition of retinal antigen. The ability of the transferred CD8+ T cells to respond to antigen in vivo was confirmed in control mice, which received an i.p. inoculation of b-gal peptide that reduced both the number and CFSE staining intensity of recovered CD8+ T cells. Furthermore, inoculation of the CD8+ T cells into ROSA26 recipients resulted in rapid loss of greater than 90% of the labeled T cells from the spleen. Finally, recovery of the CD8+ T cells was altered following inoculation into GFAP mice expressing b-gal in both the brain and several tissues of the eye. In these mice, activated CD8+ T cells could induce damage to some b-gal positive ocular tissues. Conclusion: These experiments test the ability of endogenous retinal b-gal to be processed into MHC class I in cells at a site accessible to resting CD8+ T cells. The results found with resting CD8+ T cells are consistent with antigen sequestration in that there was no response to antigen located in the retina. CR: None Support: NIH grant EY11542, Research to Prevent Blindness, MN Lions, Anna Heilmaier Fund.
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