During recent years, combined heart-lung transplantation has been increasingly performed to treat patients with end-stage pulmonary and cardiac diseases. Although through the use of cyclosporine, the transplant outcome has significantly improved, a major problem continues to be infection and rejection. In order to obtain a better understanding of the lung allograft response, we have began to study bronchoalveolar lavages (BAL) from heart-lung transplant patients. BAL is a safe procedure with minimal morbidity and can be done at several time intervals following transplantation. The presence of large numbers of cells in BAL provides unique opportunities of studying in situ immunity to lung allografts. The proposed studies deal with the analysis of the allospecificity of lymphocytes in BAL and peripheral blood. This will be done by primed lymphocytes testing (PLT) towards donor HLA antigens. We will determine the presence of donor specific cytotoxic cells recognizing class I and class II HLA antigens. Studies are designed to investigate the in vitro sensitivity of the proliferative responses of BAL lymphocytes and PBL to immunosuppressive drugs. In this investigation we will also study the interactions between lymphocytes and alveolar macrophages in BAL in relation to alloactivation and infection. The findings of these studies will be assessed for clinical relevance in particular in relation to the diagnosis of lung allograft rejection and the management of the heart-lung transplant patient.
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