Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Sledzinska, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Hemmers, Saskia UNSPECIFIED UNSPECIFIED UNSPECIFIED Mair, Florian UNSPECIFIED orcid.org/0000-0001-6732-5449 UNSPECIFIED Gorka, Oliver UNSPECIFIED orcid.org/0000-0002-8245-3008 UNSPECIFIED Ruland, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Fairbairn, Lynsey UNSPECIFIED UNSPECIFIED UNSPECIFIED Nissler, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Waisman, Ari UNSPECIFIED orcid.org/0000-0003-4304-8234 UNSPECIFIED Becher, Burkhard UNSPECIFIED orcid.org/0000-0002-1541-7867 UNSPECIFIED Buch, Thorsten UNSPECIFIED orcid.org/0000-0002-2236-9074 UNSPECIFIED
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:	Keywords Language GROWTH-FACTOR-BETA; RECEPTOR TRANSGENIC MICE; FOXP3 EXPRESSION; II RECEPTOR; TARGETED DISRUPTION; IN-VIVO; SMAD3; DIFFERENTIATION; PROLIFERATION; AUTOIMMUNITY Multiple languages Biochemistry & Molecular Biology; Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47548