T lymphocytes are formed in the thymus by a combination of positive and negative selection. This process is preceded by extensive cell division. During thymic selection, T cells change their surface markers and differentiate into mature resting cells. After leaving the thymus, mature T cells express the typical surface phenotype of naive resting cells until T cells are confronted with antigen. Contact with antigen results in T cell activation and division and causes the cells to express a new range of surface markers. Some of these activated cells eventually differentiate into cells carrying immunological memory. To seek further information on the surface markers and turnover rates of immature and mature T cells, two broad lines of investigation are proposed. First, detailed information on the events involved in positive and negative selection in the thymus will be sought with the aid of an in vitro culture system in which immature CD4+8+ T cells are induced to differentiate into mature CD4+8- and CD4-8+ cells through contact with MHC molecules expressed on dispersed thymic epithelial cells (TEC). Positive selection of T cells in this system will be studied in terms of cell surface marker expression and cell division. These studies will involve T cells from normal and T cell receptor (TCR) transgenic mice. Second, mature extrathymic T cells will be characterized with respect to their rates of division and expression of various cell surface markers. Turnover rates and surface marker expression will be examined for normal T cells and T cells from TCR transgenic mice; both alpha/beta and gamma/delta T cells will be studied. T cells are critical in combating infectious diseases and cancer, and it is essential to have a thorough understanding of how T cells are produced and how long these cells survive.
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