Our research effort involves exploring the cellular mechanisms involved in allograft rejection as well as cellular mechanisms culminating in tolerance induction. Further, we have been particularly interested in cellular immune defects in selected murine immunodeficiency models such as Murine Acquired Immunodeficiency Syndrome (MAIDS), Graft Versus Host Disease (GVHD), and Aging. Ongoing studies involve a) the role of host type Antigen Presenting Cells (APCs) in allograft rejection: we have shown by a cross-priming system that host type APCs process and present graft alloantigen to host T cells. Futur plans involve delineating the phenotype and function of the T cells that ar primed. In another project, we have further conclusively shown that CD8+ T cell depleted mice reject skin grafts differing in MHC class I expression by anti-CD8 resistant CD8+ T cells, b) using thymectomized mice which have been CD4 T cell depleted by mAb treatment in vivo, we have shown that it is possible to induce tolerance to the H-Y antigen present on male skin grafts Future experiments will define the specific mechanisms and cells involved in this process and the extension of these findings to other antigens, c) characterization of cell mediated immunity in mice with MAIDS, we have demonstrated that these infected animals have marked impairment of CD4+ T cells but no functional impairment of CD8+ T cells. Further, the skin from these animals is rejected by syngeneic hosts. Thus, epidermal cells from these animals express neo-transplantation antigens, likely of viral origin, d) characterization of cell mediated immunity in mice with GVHD: we have demonstrated that the renal disease associated with this entity has a dramatically accelerated course in female versus male animals. We are currently exploring whether this relates to host factors versus T cell innoculum, e) studies in aging mice have shown that such mice are deficient in CD4+ T cell function as demonstrated by graft rejection and CTL generation.
