The common theme which binds this Program Project together is the concerted effort to develop improved methods of regulating the immune response of human transplant recipients. Patients receiving cadaveric and living-related donor renal allografts and those receiving high risk corneal transplants will be studied. Although data will be carefully collected using new methods to define the host response to an allograft and conventional immunosuppression (Project IV), our emphasis will be upon using those data for host modification to prolong graft survival. Monoclonal anti-T cell antibodies will be used not only to characterize peripheral blood and thoracic duct lymphocyte subsets, but also as immunosuppressive agents in primates and eventually in humans (Project I). Human T-cell hybrid cell lines which produce suppressive factors or antibodies or which are themselves suppressive (or enhancing) will be developed (Project II). Initial clinical trials will utilize thoracic duct drainage, total lymphoid irradiation or total body irradiation with bone marrow reconstitution to remove or replace certain specific cellular and humoral elements while lymphocyte metabolism and cell surface properties are studied (project III). The ultimate goal of achieving specific unresponsiveness by altering the host response to human alloantigens alone will be pursued (Project V). Our effort to specifically and predictably after host immune function will require a close, collaborative effort between clinical and basic scientists. Investigators from the Duke Immunology, Surgery, Pathology, Medicine and Ophthalmology Departments will participate in this Program Project.
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