These investigations in transplatation biology have been designed to define the interrelated host immunological events, both cellular and humoral, which occur in response to vascularized organ allografts. OUr efforts are concerned primarily with elucidating and amplifying the nature, function and dynamics of cell populations and subpopulations infiltrating both acutely rejecting and long surviving allografts and understanding the events occurring concomitantly in host lymphoid tissues. These data are integrated into parallel studies defining serial changes in lymphocyte migration patterns and in morphology of lymphoid tissues following modification of the graft recipient. Using primarily the heterotopic cardiac allograft transplanted between inbred strains of rats, three recipient models are under investigation; the enhanced graft recipient, the Cyclosporin A (CyA) treated host and the B recipient. Allograft survival is prolonged markedly in all three models, indefinitely in the latter two. Acute rejection will be re-established by adoptive transfer of unsensitized and sensitized lymphocytes with or without macrophages and with or without Interleukins (IL 1 and 2). Transferred leukocytes will be fractionated into subpopulations using monoclonal antibodies and will be expanded in vitro by stimulation into allogeneic cells and/or IL-2. Specificity of these effects will be ascertained using recipients of double heart grafts from specific and third party donors. To detect their differential effects upon production of specific unresponsiveness, lymphocyte subpopulations from enhanced and CyA treated recipients will be transferred into normal sysgeneic recipients of test grafts. Immunological events in grafts and graft recipients will be examined. Thus, we will attempt serially to isolate and understand individual components of the multifaceted host responses against organ allografts and their relationships with each other. Only with more precise understanding of these host responses can selective methods of immunosuppression be devised for use in clinical organ transplantation.
Showing the most recent 10 out of 59 publications
