We propose to study two related, but distinct areas: the clinical disease, recurrent idiopathic uveitis (RIU), and an experimental model of ocular immunoregulation, trinitrophenol (TNP)-anterior chamber associated immune deviation (ACAID). Our studies in RIU are an extension of our previous work analyzing the cell surface markers on intraocular lymphocytes in chronic uveitis. Our ultimate objective is to provide a more effective means of controlling the destructive effects of recurrent inflammation in uveitis. Since our understanding of the basic pathophysiologic mechanisms in uveitis is limited, we are forced to use non-specific methods of immunosuppression (e.g., corticosteroids or chemotherapeutic agents) as treatment. We hope to provide new insight into the pathogenesis of this disease by studying ocular tissues directly. The phenotypic and functional characteristics of intraocular mononuclear cells will be analyzed, as well as the presence and role of immune complexes and other mediaters of immune responses. In addition, the possible role of viral infection will be re-explored employing modern investigative techniques. Ocular immunoregulation plays a central role in both anterior chamber immunologic privilege and recurrent uveitis. TNP-ACAID is an experimental model of ocular immunoregulation which has provided new, and important, insights into the regulatory controls generated in response to intraocular antigen. A complex suppressor cell network has been revealed which effects systemic immunity. An indepth understanding of this network, and its mediators, will open many new avenues allowing modulation of the systemic immune response. The use of a hapten (TNP)-modified protein in ACAID will allow us to study antigenic requirements for induction of suppressor responses, the site(s) in which antigen processing occurs, the soluble mediators which convey signals in the immunoregulatory network, and the effectiveness of ACAID in suppression of the ocular immune response.
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