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TGF-β Signalling Is Required for CD4(+) T Cell Homeostasis But Dispensable for Regulatory T Cell Function.
Sledzińska, Anna Hemmers, Saskia Mair, Florian Gorka, Oliver Ruland, Jürgen Fairbairn, Lynsey Nissler, Anja Müller, Werner Waisman, Ari Becher, Burkhard
Sledzińska, Anna
Hemmers, Saskia
Mair, Florian
Gorka, Oliver
Ruland, Jürgen
Fairbairn, Lynsey
Nissler, Anja
Müller, Werner
Waisman, Ari
Becher, Burkhard
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2013-10
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TGF-β is widely held to be critical for the maintenance and function of regulatory T (Treg) 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 Treg 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 Treg 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.
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TGF-β Signalling Is Required for CD4(+) T Cell Homeostasis But Dispensable for Regulatory T Cell Function. 2013, 11 (10):e1001674 PLoS Biol.
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en
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1545-7885
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