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.