TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function.
Journal Article (Journal Article)
TGF-β 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-β receptor (TR) during thymic development in mice, which leads to a lethal autoimmune syndrome. Here we describe that TGF-β-driven peripheral tolerance is not regulated by TGF-β 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-β signalling and the TR2-deficient T(reg) cells retained their suppressive function both in vitro and in vivo. In summary, absence of TGF-β 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.
Full Text
Duke Authors
Cited Authors
- Sledzińska, A; Hemmers, S; Mair, F; Gorka, O; Ruland, J; Fairbairn, L; Nissler, A; Müller, W; Waisman, A; Becher, B; Buch, T
Published Date
- October 2013
Published In
Volume / Issue
- 11 / 10
Start / End Page
- e1001674 -
PubMed ID
- 24115907
Pubmed Central ID
- PMC3792861
Electronic International Standard Serial Number (EISSN)
- 1545-7885
Digital Object Identifier (DOI)
- 10.1371/journal.pbio.1001674
Language
- eng
Conference Location
- United States