Ocular immune privilege is maintained in part by the induction of systemic regulatory T cells mediated by events that are initiated after the introduction of antigen into the Anterior Chamber. This potent (ocular) response specifically preempts the systemic induction of tissue-damaging cell-mediated immunity, some complement fixing antibodies and atopic antibodies. Accordingly, we suggest that regulatory T cells induced by intracameral antigen could be used to selectively regulate systemic autoreactive T cells. Most investigations on the induction of regulatory T cells in autoimmunity do not discriminate between the regulation of the induction of an autoimmune response and the regulation of T cells that effect autoimmunity during on-going disease. Preliminary studies by our laboratories have demonstrated that the injection of myelin basic protein or myelin oligodendrocyte glycoprotein into an anterior chamber of mice immunized to these myelin proteins induces the production of antigen-specific regulatory T cells that suppress delayed- type hypersensitivity and/or experimental allergic encephalomyelitis (EAE) effected by an encephalitogenic T cell clone. Therefore we propose that the injection of myelin proteins into an anterior chamber of mice induces T cells that specifically regulate the induction of EAE by EAE effector T cells and may modulate on-going disease. We will test this hypothesis by raising antigen-specific splenic regulatory T cells by the injection of myelin oligodendrocyte glycoprotein into an anterior chamber and (1) Test the hypothesis that antigen-specific regulatory T cells that effect and/or induce the suppression of an encephalitogenic T cells are produced (but not necessarily activated) during an immune response to the autoantigen.
This Aim will also test the hypothesis that inactive regulatory T cells are produced during an immune response to autoantigen and how these cells may be activated in vivo to prevent autoimmunity and/or eliminate an on-going autoimmune response;(2) Determine the mechanism(s) of cell-mediated suppression of EAE induced by encephalitogenic effector T cells. We will test the hypothesis that the suppression of encephalitogenic effector T cells by antigen-specific, regulatory T cells is mediated by cytokines that induce the regulatory T cells or effect suppression. The results of this study could aid our understanding of the systemic basis for the ocular regulation of autoimmunity and develop procedures for the modulation of active autoimmune disease.
