TRANSFORMED T CELL LINES FOR STUDY OF T CELL MATURATION

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Although human T cell differentiation has been studied extensively using various markers such as differentiation antigens and lectin binding properties, careful functional analysis of these T cells at the various stages of differentiation has not been carried out. This is due to the difficulties in obtaining cells from one specific stage of differentiation in sufficient pure preparations. Although interleukin-2 (IL-2) can be used to clonally expand mature T cells, immature T cells are usually not responsive to such manipulation. As an alternative approach, human T cell leukemia virus (HTLV) infected cells have been used successfully to immortalize immature T cells from a patient with severe combined immunodeficiency, as well as normal mature T cells. This method thus offers the possibility that T cells of various stages of differentiation can be transformed, cloned and studied for their functional capacities and their expression of differentiation antigens. Hybridoma technology will be used to further characterize specific antigens of these stages of T cell differentiation. Functional analysis of such cells will include the study of their ability to proliferate in response to mitogens, interleukin-1 (IL-1) and IL-2. Their ability to produce lymphokinea will be studied with IL-2 microassay, B cell proliferation assay and B cell differentiation assay. T cell differentiation and maturation in normal individuals as well as in patients with primary immunodeficiencies and bone marrow recipients will be studied. Information thus obtained will be useful in the understanding of the events leading to the maturation of T cells. It will also shed light on the defects of maturation seen in patients with immunodeficiencies. Such insights will also be of critical importance in the analysis of T cell engraftment in bone marrow recipients. (LB)