Immune Cell Infiltration into the Eye Is Controlled by IL-10 in Recoverin-Induced Autoimmune Retinopathy

• Published in: The Journal of immunology (1950) Vol. 202; no. 4; pp. 1057 - 1068
• Main Authors: Nikoopour, Enayat, Lin, Cheng-Mao, Sheskey, Sarah, Heckenlively, John R, Lundy, Steven K
• Format: Journal Article
• Language: English
• Published: United States 15.02.2019
• Subjects: Animals; Autoimmune Diseases - immunology; Eye - immunology; Eye - pathology; Inflammation - immunology; Interleukin-10 - deficiency; Interleukin-10 - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - immunology; Recoverin - immunology; Retinal Diseases - immunology; Th1 Cells - immunology; Th17 Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1800574

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 T 1 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 CD11b Ly6C 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.