The anterior chamber of the eye is endowed with remarkable properties which either prevent or significantly delay the acute rejection of various allografts. Immune privilege of the anterior chamber is a composite of several independent mechanisms which conspire to prevent the induction and execution of certain forms of inflammation. One of these mechanisms is the down-regulation of delayed-type hypersensitivity (DTH) that occurs when antigens are introduced into the anterior chamber and which has been termed anterior chamber-associated immune deviation (ACAID). ACAID appears to be an immunological compromise which protects the eye from immune-mediated injury while preserving other immune effector mechanisms that protect against life-threatening pathogens. This project will analyze the underlying mechanisms which lead to the induction of ACAID. The first specific aim will test the hypothesis that ACAID is the consequence of the preferential activation of a Th2 population which cross-regulates Th1 cells thereby inhibiting DTH. Although most antigenes induce ACAID, many do not and instead, provoke robust systemic DTH. The second specific aim will identify those characteristics which determine whether or not an antigen will induce ACAID. The third specific aim will test the hypothesis that splenic B cells reprocess antigens that are carried from the eye to the spleen. The hypothesis predicts that antigens are released by emigrating antigen presenting cells and are captured by splenic B cells which present peptide fragments to T cells leading to the generation of T suppressor cells. The long range goal of this project is to gain a clear understanding of the various immunoregulatory processes unique to the eye and which protect the delicate ocular tissues from unwitting immune-mediated injury that can lead to blindness. This information will be useful in devising strategies to either enhance immune privilege in conditions which benefit the host (e.g., corneal transplantation) or abrogate immune privilege to protect against sight- and life-threatening neoplasms.
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