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dc.contributor.authorSledzińska, Annaen
dc.contributor.authorHemmers, Saskiaen
dc.contributor.authorMair, Florianen
dc.contributor.authorGorka, Oliveren
dc.contributor.authorRuland, Jürgenen
dc.contributor.authorFairbairn, Lynseyen
dc.contributor.authorNissler, Anjaen
dc.contributor.authorMüller, Werneren
dc.contributor.authorWaisman, Arien
dc.contributor.authorBecher, Burkharden
dc.contributor.authorBuch, Thorstenen
dc.date.accessioned2013-11-14T11:04:02Z
dc.date.available2013-11-14T11:04:02Z
dc.date.issued2013-10
dc.identifier.citationTGF-β Signalling Is Required for CD4(+) T Cell Homeostasis But Dispensable for Regulatory T Cell Function. 2013, 11 (10):e1001674 PLoS Biol.en
dc.identifier.issn1545-7885
dc.identifier.pmid24115907
dc.identifier.doi10.1371/journal.pbio.1001674
dc.identifier.urihttp://hdl.handle.net/10033/305387
dc.description.abstractTGF-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.
dc.language.isoenen
dc.rightsArchived with thanks to PLoS biologyen
dc.titleTGF-β Signalling Is Required for CD4(+) T Cell Homeostasis But Dispensable for Regulatory T Cell Function.en
dc.typeArticleen
dc.contributor.departmentInstitute of Experimental Immunology, University of Zurich, Zurich, Switzerland.en
dc.identifier.journalPLoS biologyen
refterms.dateFOA2018-06-12T17:34:27Z
html.description.abstractTGF-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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