Eye‐Mediated Induction of Specific Immune Tolerance to Encephalitogenic Antigens

Abstract

Administration of antigens into the anterior chamber (AC) of the eye induces a form of antigen-specific immune tolerance termed anterior chamber-associated immune deviation (ACAID). This immune tolerance effectively impairs host delayed-type hypersensitivity (DTH) responses. We hypothesized that ACAID could be generated in BALB/c mice following AC inoculation of the encephalitogenic antigens myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). We used DTH assays and local adoptive transfer (LAT) assays to test whether MOG/MBP-induced ACAID following their administration into the AC, whether they elicited this immune tolerance via CD8(+) T cells, and whether their AC coadministration (MOG/MBP) induced specific immune tolerance to one or both antigens. We showed that MOG/MBP-induced AC-mediated specific immune tolerance, as evident from impaired DTH responses. This antigen-driven DTH suppression was solely mediated via splenic CD8(+) T cells as confirmed by LAT assays. Finally, a single AC injection with both antigens was sufficient to induce specific immune tolerance to these antigens, as evident from DTH and LAT assays. ACAID T-cell regulation could be used as a therapeutic tool in the treatment of complicated autoimmune diseases that involve multiple antigens such as multiple sclerosis.