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

• Published in: Transplant international Vol. 19; no. 5; p. 404
• Main Authors: Sun, Yimin, Ge, Bao-Sheng, Kasai, Michiyuki, Diffendaffer, Clara, Parks, Nancy, Li, Hanhan, Peng, Jianxia, Langnas, Alan N, Zhao, Yong
• Format: Journal Article
• Language: English
• Published: England 01-05-2006
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Autoantigens - chemistry; Epithelial Cells - metabolism; In Vitro Techniques; Isoantigens - chemistry; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Spleen - cytology; T-Lymphocytes, Regulatory - metabolism; Thymus Gland - metabolism; Transplantation, Homologous
• ISSN: 0934-0874
• DOI: 10.1111/j.1432-2277.2006.00300.x

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 naïve BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse antigens. BALB/c nude mice that received naïve 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.