Regulatory effects in vitro by thymic medullary epithelial cells on TCR transgenic T cells specific for male H-Y antigens.

To evaluate the ability of thymic epithelial cells (TEC) to influence growth and differentiation of antigen specific T cells, we have used female transgenic (TG) mice expressing a receptor on the majority of their T cells for the male (H-Y) antigen in the context of H-2Db antigens. Male or female TEC expanded in serum-free medium were co-cultured with female TG thymocytes. FAC-Scan analysis after 3 days of co-culture did not indicate any selective deletion of subpopulations induced by male TEC. In contrast, the presence of TEC in TG thymocyte cultures led to increased proliferation, irrespective of the type of TEC and stimulus used. Limiting dilution (LD) proliferation analyses, using irradiated male spleen cells as stimulator cells, showed increased clonability of CD4-CD8+ cells, but reduced clonability of CD4-CD8- thymocytes, in the presence of both male and female TEC. Clones from the LD cultures were expanded for several weeks. Expanded clones all expressed the v beta 8.2+ TG TCR. One-half of the expanded TG CD8+ T cell clones obtained from LD cultures exhibited H-Y specific proliferation, and the majority of clones showed antigen-specific IL-3 secretion. Expanded clones did not develop into a cytotoxic machinery in the present culture system.