| First Author | Carrier Y | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 1 | Pages | 172-8 |
| PubMed ID | 17182552 | Mgi Jnum | J:141942 |
| Mgi Id | MGI:3820048 | Doi | 10.4049/jimmunol.178.1.172 |
| Citation | Carrier Y, et al. (2007) Th3 cells in peripheral tolerance. II. TGF-beta-transgenic Th3 cells rescue IL-2-deficient mice from autoimmunity. J Immunol 178(1):172-8 |
| abstractText | We developed a transgenic (Tg) mouse that expresses TGF-beta under control of the IL-2 promoter to investigate Th3 cell differentiation both in vitro and in vivo. We previously found that repetitive in vitro Ag stimulation results in constant expression of Foxp3 in TGF-beta-Tg Th3 cells that acquire regulatory function independent of surface expression of CD25. To examine the differentiation and function of Th3 cells in vivo and to compare them with thymic-derived CD4(+)CD25(+) regulatory T cells (Treg), we introduced the TGF-beta transgene into T cells of IL-2-deficient (IL-2(-/-)) mice. We found that the induction, differentiation, and function of TGF-beta-derived Foxp3(+) Th3 cells were independent of IL-2, which differs from thymic Tregs. In an environment that lacks functional CD25(+) thymic-derived Tregs, expression of the TGF-beta transgene in IL-2(-/-) mice led to the induction of distinct CD25(-) regulatory cells in the periphery. These cells expressed Foxp3 and efficiently controlled hyperproliferation of T cells and rescued the IL-2(-/-) mouse from lethal autoimmunity. Unlike IL-2(-/-) animals, TGF-beta/IL-2(-/-) mice had normal numbers of T cells, B cells, macrophages, and dendritic cells and did not have splenomegaly, lymphadenopathy, or inflammation in multiple organs. Accumulation of Foxp3(+) cells over time, however, was dependent on IL-2. Our results suggest that TGF-beta-derived Foxp3(+)CD25(+/-) Th3 regulatory cells represent a different cell lineage from thymic-derived CD25(+) Tregs in the periphery but may play an important role in maintaining thymic Tregs in the peripheral immune compartment by secretion of TGF-beta. |
