The overall aims of the present proposal are directed at the isolation and characterization of unique and still poorly characterized subpopulations of human T lymphocytes with the view that such cells may be centrally involved in the circuits which both up and down regulate the human immune response. The intention is to take advantage of major recent developments in methods for the generation of antibodies to cell surface antigens, for the isolation of purified subpopulations of cells, for the cloning of distinct populations of cells, and lastly for newer methods for the functional analysis of these populations of cells. In the present studies, we plan to undertake a detailed analysis of the phenotypic and functional properties of unique subpopulations of human T lymphocytes. In particular, we plan to develop monoclonal antibody probes to cell surface molecules which can divide the human inducer and suppressor populations into distinct subsets. To accomplish this, we plan to develop immunization and screening strategies which utilize primate lymphocyte populations, subsets of human peripheral T cells and cloned populations of functionally unique populations of human T cell lines. Once these antibodies are identified, we will separate both the inducer and suppressor populations into phenotypically unique subsets and investigate each for their regulatory effects on other human T, B and myeloid cells. The antibodies defined above will be utilized to characterize biochemically the cell surface structures they define. Moreover, attempts will be made to elucidate the function of the structures characterized. These antibodies will be useful in dissecting and characterizing patients with autoimmune and immunodeficiency diseases where the immunoregulatory circuit is clearly abnormal. Lastly, we will identify minor populations of T lymphocytes present both in normal peripheral blood and which can be cultured and determine whether these minor populations have distinct and unique functional programs.

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National Institute of Allergy and Infectious Diseases (NIAID)
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Allergy and Immunology Study Section (ALY)
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Dana-Farber Cancer Institute
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