REGULATORY EVENTS IN T CELL DEVELOPMENT IN THE THYMUS

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Increasing evidence suggests important events in T cell maturation in the thymus are governed by specific gene regulation. In the thymus, precursor cells undergo a complex set of developmental events and emerge as mature T lymphocytes capable of specific antigen recognition. We have found that gene expression varies at different stages of thymic development both in a variety of transformed cell lines that represent discrete stages of thymic development as well in fetal thymocytes harvested directly from mouse fetuses. We are focusing on regulation of the genes for IL-2 and IL-2 receptor alpha and beta chains together with the function of various transcriptional transactivators. To do so, we have developed a method to introduce exogenous DNA into thymocytes in intact thymic lobes. During cultivation of such lobes in vitro, normal developmental changes take place allowing us to study gene regulatory changes dynamically. We are also trying to identify gene products associated with the commitment to the T cell lineage.