| First Author | Sledzińska A | Year | 2013 |
| Journal | PLoS Biol | Volume | 11 |
| Issue | 10 | Pages | e1001674 |
| PubMed ID | 24115907 | Mgi Jnum | J:204579 |
| Mgi Id | MGI:5532851 | Doi | 10.1371/journal.pbio.1001674 |
| Citation | Sledzinska A, et al. (2013) TGF-beta signalling is required for CD4(+) T cell homeostasis but dispensable for regulatory T cell function. PLoS Biol 11(10):e1001674 |
| abstractText | TGF-beta is widely held to be critical for the maintenance and function of regulatory T (T(reg)) cells and thus peripheral tolerance. This is highlighted by constitutive ablation of TGF-beta receptor (TR) during thymic development in mice, which leads to a lethal autoimmune syndrome. Here we describe that TGF-beta-driven peripheral tolerance is not regulated by TGF-beta signalling on mature CD4(+) T cells. Inducible TR2 ablation specifically on CD4(+) T cells did not result in a lethal autoinflammation. Transfer of these TR2-deficient CD4(+) T cells to lymphopenic recipients resulted in colitis, but not overt autoimmunity. In contrast, thymic ablation of TR2 in combination with lymphopenia led to lethal multi-organ inflammation. Interestingly, deletion of TR2 on mature CD4(+) T cells does not result in the collapse of the T(reg) cell population as observed in constitutive models. Instead, a pronounced enlargement of both regulatory and effector memory T cell pools was observed. This expansion is cell-intrinsic and seems to be caused by increased T cell receptor sensitivity independently of common gamma chain-dependent cytokine signals. The expression of Foxp3 and other regulatory T cells markers was not dependent on TGF-beta signalling and the TR2-deficient T(reg) cells retained their suppressive function both in vitro and in vivo. In summary, absence of TGF-beta signalling on mature CD4(+) T cells is not responsible for breakdown of peripheral tolerance, but rather controls homeostasis of mature T cells in adult mice. |
