Rapamycin Suppresses T Cell Responses in Recoverin-Induced Autoimmune Retinopathy and Prevents Disease Progression in the Eyes

Abstract Autoimmune retinopathy (AIR) causes acute and progressive vision loss in patients. We have established a murine model using the retinal autoantigen, recoverin, to better understand the immunopathology of AIR. Immunization of C57BL6 mice with recombinant mouse recoverin resulted in systemic recoverin-specific Th1 and Th17 cell responses and infiltration of CD4+ and CD8+ T lymphocytes, B lymphocytes, and CD11b+Ly6C+ inflammatory monocytes into the eyes. Treatment of mice with rapamycin at the time of immunization suppressed the induction of recoverin immunity and reduced inflammation in the eyes compared to the untreated group. Rapamycin dampened Th1 and Th17 T cell responses in draining lymph nodes and lowered serum antibody titers toward recoverin. There was a significant decrease in the number of CD4+ T cells and CD11b+Ly6C+ inflammatory monocytes infiltrating the eyes of rapamycin-treated mice. A higher number of CD103+CD8+ tissue resident memory T cells were present in the eyes of rapamycin treated mice. Treatment resulted in a significant decrease in the frequency of CD122+CD69−PD-1−CD8+ and the total number of CD44+CD62L+ memory T cells in lymphoid organs. While adoptive transfer of T cells from recoverin-immunized mice into naïve mice led to pathological changes in the eye, adoptive transfer of T cells from a rapamycin treated group did not result in eye pathology in the recipient. Treatment of mice with rapamycin at later time points after disease induction did not prevent disease, however, transfer of recoverin-specific T cells from those mice into recipient mice failed to induce disease. Our findings indicate rapamycin may be an effective drug for suppression of autoimmune retinopathy in some circumstances.