Sledzinska, Anna, Hemmers, Saskia, Mair, Florian ORCID: 0000-0001-6732-5449, Gorka, Oliver ORCID: 0000-0002-8245-3008, Ruland, Juergen, Fairbairn, Lynsey, Nissler, Anja, Mueller, Werner, Waisman, Ari ORCID: 0000-0003-4304-8234, Becher, Burkhard ORCID: 0000-0002-1541-7867 and Buch, Thorsten ORCID: 0000-0002-2236-9074 (2013). TGF-beta Signalling Is Required for CD4(+) T Cell Homeostasis But Dispensable for Regulatory T Cell Function. PLoS. Biol., 11 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1545-7885

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sledzinska, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemmers, SaskiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mair, FlorianUNSPECIFIEDorcid.org/0000-0001-6732-5449UNSPECIFIED
Gorka, OliverUNSPECIFIEDorcid.org/0000-0002-8245-3008UNSPECIFIED
Ruland, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fairbairn, LynseyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nissler, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, WernerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waisman, AriUNSPECIFIEDorcid.org/0000-0003-4304-8234UNSPECIFIED
Becher, BurkhardUNSPECIFIEDorcid.org/0000-0002-1541-7867UNSPECIFIED
Buch, ThorstenUNSPECIFIEDorcid.org/0000-0002-2236-9074UNSPECIFIED
URN: urn:nbn:de:hbz:38-475483
DOI: 10.1371/journal.pbio.1001674
Journal or Publication Title: PLoS. Biol.
Volume: 11
Number: 10
Date: 2013
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1545-7885
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GROWTH-FACTOR-BETA; RECEPTOR TRANSGENIC MICE; FOXP3 EXPRESSION; II RECEPTOR; TARGETED DISRUPTION; IN-VIVO; SMAD3; DIFFERENTIATION; PROLIFERATION; AUTOIMMUNITYMultiple languages
Biochemistry & Molecular Biology; BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47548

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