The eye has interactions with the systemic immune system that differ from those at other anatomic sites. The anterior chamber has been known to be a privileged site since the finding that allogeneic tissue implants placed there survive longer than at other sites. This has allowed of the clinical use of corneal allotransplants, although rejection can occur if vascularization of the allograft ensues. The ability of the eye to serve as an organ for the induction of immune responses has been examined in animal models by the placement of immunogenic haptens coupled to syngeneic cells, allografts, or certain tumor cells into sites in the eye. Although this approach has yielded significant information, it has not elucidated the mechanisms by which resident cells function in the eye to initiate or regulate an immune response. This application proposes to examine the ability of various populations of ocular cells (OC) from the interior of the eye to serve as antigen presenting cells for the induction of immunity and/or immunologic suppression in a murine system. Preliminary studies have shown that a mixed population of OC (MOC) from inside the anterior murine eye are capable of inducing T suppressor (Ts) cells in a hapten system. This activity appears to reside in cells bearing the I-A antigen. Proposals outlined in this application are to phenotypically characterize the subsets of MOC involved in the activation of Ts cells and to determine in what anatomic sites they reside, to examine the ability of OC from various ocular compartments to present antigens in vitro to primed and unprimed T cells and for the induction of in vivo immunity, and to determine the morphologic and immunohistologic characteristics of OC in situ. By comparing immunohistochemical data with the surface phenotype of cell subsets involved in the activation of suppression or immunity obtained from functional studies, the cellular and anatomic identity of these subsets may be elucidated. Other studies will examine the ability of populations of OC to produce interleukin 1, interleukin 2, interleukin 3, or inhibitors of these cytokines. Teleologically, it would seem important that animals have mechanisms to limit inflammation and immunologic reactivity in the eye in order to preserve the transparency of light- transmitting structures. Thus, a search for immunologic modulators produced by OC Is warranted. Elucidation of the mechanisms of immunologic privilege of the eye might have currently unforseen therapeutic implications, particularly in allotransplantation.
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