Clinical observations support the notion that the immune system may be important in the control of various categories of intraocular tumors. The present research plan will use in vivo and in vitro procedures to identify specific immune processes involved in spontaneous resolution of intraocular """"""""regressor"""""""" tumors in mice. The role of delayed-type hypersensitivity (DTH), cytotoxic T-lymphocytes (CTL), and antibody will be analyzed independently in mice with selective immunologic impairments (e.g., Lyt 1- and Lyt 2- phenotypes) and by in vitro assays. Histopathological and immunohistological analyses will be used to confirm or refute the immunological conclusions. Collectively, these studies should provide important insights into the mechanisms of spontaneous rejection of intraocular tumors. By understanding these processes it may be possible to devise immunotherapeutic procedures to induce or hasten spontaneous rejection of intraocular tumors in humans. The second part of this research plan will focus on the mechanisms responsible for immune privilege in the anterior chamber of the eye. The investigators will characterize the mechanisms that prevent normal allograft rejection within the anterior chamber. Immunological, histopathological, and immunohistological procedures, similar to those described above, will be used to unravel the mystery of immune privilege in the anterior chamber and provide clues for applying this process to therapeutic transplants. The same mechanisms that sustain allograft survival within the anterior chamber might be involved in the longterm survival of therapeutic keratoplasties. Studies will determine if corneal tissues are susceptible to immune rejection by DTH, CTL, or antibody-mediated processes in vivo. These studies will also examine the possibility that anterior chamber presentation of corneal antigens evokes a unique suppression of systemic cellular immunity that in turn prevents corneal allograft rejection. Results from these studies will not only expand our understanding of corneal transplantation but might have therapeutic applications.
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