Role of the thymic environment in T-cell differentiation
What is the role of the thymic environment in T cell differentiation? Interactions between T lymphocyte progenitors or their immature progeny and non-lymphoid stromal cells comprising the thymic environment play a central role in T cell differentiation. These interactions may involve soluble factors produced by stromal cells or cellular interactions involving receptor-mediated recognition of cell surface molecules. Mechanisms of the latter type are thought to be central to both the establishment of genetically restricted T cell antigen recognition (positive selection) and clonal elimination of self-reactive T cells (negative selection).
One approach to this question has involved the definition of thymic stromal cell heterogeneity in terms of cell surface molecules unique to discrete subpopulations of thymic stromal cells and the establishment of thymic stromal cell lines reflecting this heterogeneity. A panel of monoclonal antibodies raised against thymic stroma is being used to biochemically characterize stromal cell surface molecules and to characterize the lineage of different stromal cell lines. These thymic stromal cell lines are being tested for their ability to support the differentiation of T cell progenitors in vitro. In a related approach, fetal thymus organ cultures and reaggregate cultures with thymocytes and thymic stromal cell lines are being used to define the important cellular interactions, cell interaction molecules and cytokines involved in thymic organogenesis and thymocyte development.