IMMUNOPATHOGENESIS OF CHRONIC CARDIAC GRAFT REJECTION

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We propose an integrated, multi-disciplinary research program of basic and clinical research with an overall objective to determine the role of T cells in the pathogenesis of chronic rejection of cardiac allografts and to develop new approaches for prevention of chronic rejection by inducing, in athe T cells of the recipient, tolerance to the cardiac allograft. This will be accomplished by evaluating whether infusion of donor bone marrow will prevent or reduce the severity of graft arteriosclerosis (GA) in human cardiac allografts by increasing microchimerism and inducing antigen- specific tolerance. This Program Project is based on extensive stat e-of-the-art expertise in human T-cell immunology in the Department of Microbiology and Immunology of Temple University School of Medicine and on an extensive and very successful clinical adult heart transplantation program at Temple University Hospital, which is the busiest in the United States. Seventy six heart transplants were performed in 1994 at Temple University health Sciences. As of October 12, 1995 sixty five heart transplants have already been performed. This Program Project is comprised of Research Projects: 1. The role of T cells in the pathogenesis of chronic rejection is addressed, 2. The role of cytokines in the development of GA is addressed. 3. The objective of the third Research Project is to determine whether administration of donor bone marrow prevents or reduces the incidence and severity of GA in cardiac transplant recipients and increases microchimerism. These interactive studies are supported by a Clinical Transplantation Core and an Administrative Core. The Clinical Transplantation Core includes a consortium arrangement with Dr. C. Ricordi of the University of Miami, School of Medicine.