Skip to main content
Journal cover image

TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function.

Publication ,  Journal Article
Sledzińska, A; Hemmers, S; Mair, F; Gorka, O; Ruland, J; Fairbairn, L; Nissler, A; Müller, W; Waisman, A; Becher, B; Buch, T
Published in: PLoS Biol
October 2013

TGF-β 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-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 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-β signalling and the TR2-deficient T(reg) 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

October 2013

Volume

11

Issue

10

Start / End Page

e1001674

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Thymus Gland
  • Tamoxifen
  • T-Lymphocytes, Regulatory
  • Signal Transduction
  • Reproducibility of Results
  • Receptors, Antigen, T-Cell
  • NIH 3T3 Cells
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sledzińska, A., Hemmers, S., Mair, F., Gorka, O., Ruland, J., Fairbairn, L., … Buch, T. (2013). TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. PLoS Biol, 11(10), e1001674. https://doi.org/10.1371/journal.pbio.1001674
Sledzińska, Anna, Saskia Hemmers, Florian Mair, Oliver Gorka, Jürgen Ruland, Lynsey Fairbairn, Anja Nissler, et al. “TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function.PLoS Biol 11, no. 10 (October 2013): e1001674. https://doi.org/10.1371/journal.pbio.1001674.
Sledzińska A, Hemmers S, Mair F, Gorka O, Ruland J, Fairbairn L, et al. TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. PLoS Biol. 2013 Oct;11(10):e1001674.
Sledzińska, Anna, et al. “TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function.PLoS Biol, vol. 11, no. 10, Oct. 2013, p. e1001674. Pubmed, doi:10.1371/journal.pbio.1001674.
Sledzińska A, Hemmers S, Mair F, Gorka O, Ruland J, Fairbairn L, Nissler A, Müller W, Waisman A, Becher B, Buch T. TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. PLoS Biol. 2013 Oct;11(10):e1001674.
Journal cover image

Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

October 2013

Volume

11

Issue

10

Start / End Page

e1001674

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Thymus Gland
  • Tamoxifen
  • T-Lymphocytes, Regulatory
  • Signal Transduction
  • Reproducibility of Results
  • Receptors, Antigen, T-Cell
  • NIH 3T3 Cells
  • Mice, Inbred C57BL
  • Mice