The objectives of the proposed research are to establish animal models of different types of orbital lymphoproliferative and granulomatous inflamation, in order to elucidate the basic immunologic mechanisms in the induction of these ocular diseases, and to develop methods to prevent or suppress them by manipulating the immune system. An experimental model of immunogenic pseudotumor of the orbit in inbred rats has recently been developed. This model involves the administration of insoluble beads coated with antigen in the orbital tissue of previously immunized rats. The resulting chronic granuloma was shown to be a T cell-mediated response.
The specific aim of the proposed study is to explore methods to prevent or suppress such harmful inflammation, using syngeneic cell-bound antigens to induce suppressor cell activity, and T lymphoblasts to confer protective anti-idiotypic immunity. An experimental model of pseudotumorous dacryoadenitis has also been developed which involves the induction of a spontaneous lymphoproliferative disease by immunizing rats to an organ-specific antigen of the lacrimal gland. The resulting lesions have many features in common with those present in human disease. Efforts will be made to isolate, purify, chemically characterize, and topographically localize the autoantigen responsible, to aid in better understanding the basic pathogenetic mechanisms of this autoimmune disease. Using in vitro cytotoxicity assays and passive transfer experiments, attempts will be made to define the immunological mechanisms that cause this lymphoproliferative disease. Specifically, these studies will define more precisely the nature of the damaging autoimmune reactions participating in this ocular disease, to characterize the types of cells that trigger and mediate the inflammatory response, and to define the role of T cells or B cells in this autoallergic reaction.
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