IMMUNOBIOLOGY OF THE ACQUIRED IMMUNODEFICIENCY SYNDROME

During the last several years, this laboratory has been intimately involved in the development of human lymphocyte cell separation procedures, human lymphocyte functional assays, cell cloning strategies and assessment of T cell surface molecules using monoclonal antibodies that together permit precise analysis of human immune responses in vitro. The thrust of the current proposal is to bring to bear these technologies as well as the resulting newer insights into human T cell differentiation and function to the analysis of lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS). Control populations will include normal individuals as well as patients with acute viral infections and patients with acquired hypogammaglobulinemia (AHG). The latter syndrome is a mirror image of the AIDS syndrome in that whereas patients with AIDS in vivo have no DTH responses and are hypergammaglobulinemic, patients with AHG have brisk DTH responses but are hypogammaglobulinemic. Specifically, our aims are to isolate and functionally characterize, in detail, T4+ and T8+ subsets from AIDS patients and controls with particular attention to the analysis of T-T, T-B and T-macrophage interactions. In addition, we will analyze cell surface activation molecules of human T cells in AIDS cells, prepare new monoclonal antibodies to isolated AIDS T4 and T8 sets in order to define unique (defective) subsets and finally clone unique subsets from AIDS patients in order to study these cells in precise immunobiologic terms. The AIDS syndrome is a unique model of a human immunodeficiency syndrome that unfortunately is not rare and occurs in young adults from whom sufficient numbers of lymphocytes can be studied. Data concerning the basic functions of AIDS lymphocytes will have broad implications relevant to the analysis of immune defects in cancer, autoimmunity and control of viral and fungal infections.