In Vivo Generation Of Autoantigen-Specific Treg Cells In Treating Experimental Autoimmune Uveitis Without Compromising Anti-Tumor Immunity

Generation of autoantigen-specific regulatory T (Treg) cells that suppress tissue-specific autoimmunity without compromising beneficial immune responses is the holy-grail for immunotherapy to autoimmune diseases. In a model of experimental autoimmune uveitis (EAU), we show here that we successfully generated retinal autoantigen-specific Treg cells in vivo by inducing CD4+ T cell apoptosis with antibody followed by administration of retinal autoantigen peptides (e.g., interphotoreceptor retinoid-binding protein) in mice with established EAU. We demonstrated that the therapeutic approach resulted in long-term remission of ocular inflammation and rescue of retinal function in the eyes of the mice with EAU. Mechanistically, this therapeutic effect was mediated by the generation of retinal antigen-specific Treg cells that inhibited uveitogenic Th17 response in TGF-β and IL-10 dependent manner. Importantly, these tolerized mice did not compromise their anti-tumor immunity in a model of melanoma. Thus, we have discovered a specific immunotherapy of EAU by in vivo generation of retinal antigen-specific Treg cells, which should have implication for patients with autoimmune uveitis.