The eye is protected from destructive innate and adaptive immune mechanisms by a local environment that is not conducive to immune-mediated reactions and by the ocular-induced regulation of systemic immunity. Active systemic regulation of destructive cell-mediated immunity is mediated by Anterior Chamber-Associated Immune Deviation (ACAID) imposed on the systemic immune system by complex cellular pathways in which circulating antigen presenting cells home to the thymus and to the spleen. In the thymus and spleen T lymphocytes that induce and effect the suppression of cell-mediated immunity are produced. Our laboratory has shown that after the intracameral injection of antigen (i) intracameral antigen but not intravenous antigen is found in the thymus;(ii) both iris monocytic cells and similar circulating monocytic cells activate immunoregulatory NK 1.1+ thymocytes that (i) enhance the production of lgG1 antibodies to the intracameral antigen and activate CD4+ and CD8+ splenic T cells that suppress cell-mediated immunity. To advance these studies we propose that the intracameral injection of antigen induces monocytic cells in the iris/ciliary body that activate thymic regulatory T cells and splenic immunoregulatory T cells that suppress systemic delayed-type hypersensitivity. To test this hypothesis we will (1) determine the mechanisms(s) by which intracameral antigen travels to the thymus and spleen, (2) determine the induction of regulatory thymocytes by monocytic cells derived from the iris. (3) Determine the mechanism(s) by which immunoregulatory thymocytes from donors receiving intracameral antigen activate splenic suppressor T cells. These studies are essential to a full definition of an oculo/thymic/splenic axis. This ocular-thymic link confirms an active role for the thymus and the eye in the regulation of systemic immunity that could impact on the management of inflammatory eye disease, corneal transplantation, ocular tumors and autoimmune disease. ? ? ? ?
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