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Tumor suppressor TSC1 is critical for T-cell anergy.

Publication ,  Journal Article
Xie, D-L; Wu, J; Lou, Y-L; Zhong, X-P
Published in: Proc Natl Acad Sci U S A
August 28, 2012

T-cell anergy is a state of T cells that is hyporesponsive to stimulation via the T-cell receptor and costimulatory molecules and is thought to be important for self-tolerance. How T-cell anergy is regulated is still poorly understood. We report here that tuberous sclerosis (TSC)1 is critical for T-cell anergy. Deficiency of TSC1 resulted in enhanced T-cell proliferation and cytokine production in the absence of cluster of differentiation (CD)28-mediated costimulation, accompanied by enhanced T-cell metabolism. Resistance of TSC1-deficient T cells to anergy is correlated with increased signaling through the mammalian target of rapamycin complex (mTORC)1 and can be reverted by treatment of these cells with mTORC1 inhibitor rapamycin. Expression of the inducible costimulator (ICOS) is increased in TSC1-deficient T cells, which can be inhibited by rapamycin. Simultaneous blockade of both CD28 and ICOS costimulation partially restored sensitivity of TSC1-deficient T cells to anergy induction. Together, our data indicate that TSC1 is crucial for T-cell anergy by inhibiting mTORC1 signaling through both ICOS-dependent and -independent mechanisms.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 28, 2012

Volume

109

Issue

35

Start / End Page

14152 / 14157

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tuberous Sclerosis Complex 1 Protein
  • TOR Serine-Threonine Kinases
  • T-Lymphocytes
  • Signal Transduction
  • Proteins
  • Multiprotein Complexes
  • Mice, Knockout
  • Mice
  • Mechanistic Target of Rapamycin Complex 1
 

Citation

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Xie, D.-L., Wu, J., Lou, Y.-L., & Zhong, X.-P. (2012). Tumor suppressor TSC1 is critical for T-cell anergy. Proc Natl Acad Sci U S A, 109(35), 14152–14157. https://doi.org/10.1073/pnas.1119744109
Xie, Dan-Li, Jinhong Wu, Yong-Liang Lou, and Xiao-Ping Zhong. “Tumor suppressor TSC1 is critical for T-cell anergy.Proc Natl Acad Sci U S A 109, no. 35 (August 28, 2012): 14152–57. https://doi.org/10.1073/pnas.1119744109.
Xie D-L, Wu J, Lou Y-L, Zhong X-P. Tumor suppressor TSC1 is critical for T-cell anergy. Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):14152–7.
Xie, Dan-Li, et al. “Tumor suppressor TSC1 is critical for T-cell anergy.Proc Natl Acad Sci U S A, vol. 109, no. 35, Aug. 2012, pp. 14152–57. Pubmed, doi:10.1073/pnas.1119744109.
Xie D-L, Wu J, Lou Y-L, Zhong X-P. Tumor suppressor TSC1 is critical for T-cell anergy. Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):14152–14157.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 28, 2012

Volume

109

Issue

35

Start / End Page

14152 / 14157

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tuberous Sclerosis Complex 1 Protein
  • TOR Serine-Threonine Kinases
  • T-Lymphocytes
  • Signal Transduction
  • Proteins
  • Multiprotein Complexes
  • Mice, Knockout
  • Mice
  • Mechanistic Target of Rapamycin Complex 1