THYMIC ENVIRONMENT AND T CELL DIFFERENTIATION

这项工作将采用单克隆抗体特异性针对不同

The work will employ monoclonal antibodies specific for different populations of thymic epithelial (TE) cells to pursue two aims central to our understanding the thymic role in T cell differentiation: 1) Characterize the stromal cells comprising the cortical and medullary areas of the thymus and identify antigens unique to each area which may be involved in thymocyte-epithelial cell interactions; and 2) Examine the effects of monoclonal antibodies specific for either cortical medullary TE cells on the ability of thymus organ cultures to support thymic lymphopoiesis and the generation of immuncompetent T cells in vitro. A panel of monoclonal antibodies has been generated which exhibit at least four basic labelling patterns when applied to frozen sections of thymus at the light microscopic level: all stromal cells throughout the cortex and medulla; medullary stromal cells; cortical stroma cells; and mesenchymal elements (connective tissue and vascular structures). Ultrastructural immunohistochemical studies of the thymus with these antibodies will provide a detailed characterization of epithelial compartmentalization and heterogeneity within the thymus. These studies will be complemented with biochemical analyses of the molecules recognized by these antibodies, thereby providing a description of the antigenic features of cortical and medullary environments of the thymus. Finally these antibodies will be tested for their ability to affect the function of fetal thymus organ cultures in vitro. Parameters of thymus function to be examined will include the extent of lymphopoiesis and the appearance of thymocyte populations bearing distinct Lyt-2 and L3T4 phenotypes. In addition, the ability of antibody-treated thymus organ cultures to generate immunocompetent thymocytes, resembling peripheral T cells, will be examined by a number of functional assays. These studies will contribute significantly to our understanding of T cell differentiation and address the role of different populations of TE cells in this complex process. Information obtained in this study may also prove to be valuable in understanding developmental defects of the thymus and the process of thymus involution, where the latter is accompanied by an age-related loss of thymus function in man.