TGF-β Signalling Is Required for CD4(+) T Cell Homeostasis But Dispensable for Regulatory T Cell Function.

2.50
Hdl Handle:
http://hdl.handle.net/10033/305387
Title:
TGF-β Signalling Is Required for CD4(+) T Cell Homeostasis But Dispensable for Regulatory T Cell Function.
Authors:
Sledzińska, Anna; Hemmers, Saskia; Mair, Florian; Gorka, Oliver; Ruland, Jürgen; Fairbairn, Lynsey; Nissler, Anja; Müller, Werner; Waisman, Ari; Becher, Burkhard; Buch, Thorsten
Abstract:
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.
Affiliation:
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Citation:
TGF-β Signalling Is Required for CD4(+) T Cell Homeostasis But Dispensable for Regulatory T Cell Function. 2013, 11 (10):e1001674 PLoS Biol.
Journal:
PLoS biology
Issue Date:
Oct-2013
URI:
http://hdl.handle.net/10033/305387
DOI:
10.1371/journal.pbio.1001674
PubMed ID:
24115907
Type:
Article
Language:
en
ISSN:
1545-7885
Appears in Collections:
publications of the division experimentelle Immunologie (EXIM)

Full metadata record

DC FieldValue Language
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.en
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

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.