Patients from the renal transplantation program of the Brigham and Women's Hospital will be the principal objects of intensive study of the immuno-regulatory phenomena involved in the spectrum of host responses ranging from rejection to acceptance of grafts. Some patients will be studied prior to transplantation as they receive specific preconditioning with blood transfusion, while they and others will be followed through their early transplant experience during quiescent, rejection and recovery phases. Therapy with monoclonal antibodies directed to specific lymphocyte subsets will be evaluated against the background of conventional therapies and a variety of functional and phenotypic marker studies. Cellular responses to be measured include donor-specific reactivity in mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) as well as assessment of cells which suppress these reactivities. In addition, directly reacting cytotoxic T cells (lymphocyte-mediated cytotoxicity-LMC) and antibody activity (complement-dependent and ADCC) to donor cells will be measured. Patient lymphocytes will not only be phenotyped for the well established monoclonal markers of helper/inducer and cytotoxic/suppressor cells, but a new generation of monoclonals which define further subsets as well as states of activation will be employed to determine which subset is activated and/or in DNA synthesis, utilizing dual laser flow cytometry. Monitoring of the phenotypes of cells in graft infiltrates will be an important component of the study. Selected examples of patients receiving corneal allografts will also be studied to determine whether there are any fundamental differences with a different tissue, and in the absence of immunosuppression. Knowledge gained from these studies should have broad application to other problems in clinical immunology.
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