Autoimmune retinopathy (AIR) is a treatable condition that manifests in acute and progressive vision loss in patients. It has recently been determined that AIR is associated with an imbalance of T1 versus regulatory T cell immunity toward the retinal protein， recoverin. This study describes a new murine model to understand the immunopathology of AIR and its association with T cell responses toward recoverin. Immunization of C57BL/6 mice with recoverin resulted in ocular inflammation including infiltration of CD4 and CD8 T lymphocytes， B cells， and CD11bLy6C inflammatory monocytes in the eyes. Production of IFN-γ and IL-17 from T cells was exacerbated in IL-10 knockout (KO) mice and kinetics of disease de... More
Autoimmune retinopathy (AIR) is a treatable condition that manifests in acute and progressive vision loss in patients. It has recently been determined that AIR is associated with an imbalance of T1 versus regulatory T cell immunity toward the retinal protein， recoverin. This study describes a new murine model to understand the immunopathology of AIR and its association with T cell responses toward recoverin. Immunization of C57BL/6 mice with recoverin resulted in ocular inflammation including infiltration of CD4 and CD8 T lymphocytes， B cells， and CD11bLy6C inflammatory monocytes in the eyes. Production of IFN-γ and IL-17 from T cells was exacerbated in IL-10 knockout (KO) mice and kinetics of disease development was accelerated. Infiltration of T cells and inflammatory monocytes into the eyes dramatically increased in recoverin-immunized IL-10 KO mice. An immunodominant peptide of recoverin， AG-16， was capable of inducing disease in IL-10 KO mice and resulted in expansion of AG-16 tetramer-specific CD4 T cells in lymphoid organs and eyes. Adoptive transfer of recoverin-stimulated cells into naive mice was sufficient to induce AIR， and immunization of B cell-deficient mice led to a milder form of the disease. This model supports the hypothesis that recoverin-specific T cell responses are major drivers of AIR pathogenesis and that IL-10 is an important factor in protection.
