Induction of regulatory T cells from mature T cells by allogeneic thymic epithelial cells in vitro

The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be regulatory T cells has not been addressed. In the present study, this issue was directly investigated by co-culturing of mature T cells and allo-TECs. B6 macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in vitro. However, BALB/c splenocytes precultured with B6-derived TECs 1-4C18 or 1C6 did not proliferate to B6 antigens, but responded to rat antigens. Exogenous interleukin-2 (IL-2) failed to revise the unresponsiveness of these T cells. Allo-TEC-cultured T cells predominantly expressed Th2 cytokines (IL-4 and IL-10). B6 TEC-cultured BALB/c splenocytes markedly inhibited the immune responses of naive BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse antigens. BALB/c nude mice that received naive syngeneic splenocytes rejected B6 or rat skin grafts by 17 days postskin grafting; however, co-injection of B6 TEC-cultured BALB/c splenocytes significantly delayed B6 skin graft rejection (P < 0.01), with the unchanged rejection of rat skin grafts. These studies demonstrate that allo-TECs are able to 'educate' mature T cells to be regulatory cells, and suggest that regulatory cells derived from mature T cells by TECs may play an important role in T cell tolerance to allo- and auto-antigens.