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Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression.

Publication ,  Journal Article
Chen, Y; Shen, S; Gorentla, BK; Gao, J; Zhong, X-P
Published in: J Immunol
February 15, 2012

Regulatory T cells (Treg) are crucial for self-tolerance. It has been an enigma that Treg exhibit an anergic phenotype reflected by hypoproliferation in vitro after TCR stimulation but undergo vigorous proliferation in vivo. We report in this study that murine Treg are prone to death but hyperproliferative in vitro and in vivo, which is different from conventional CD4(+)Foxp3(-) T cells (Tcon). During in vitro culture, most Treg die with or without TCR stimulation, correlated with constitutive activation of the intrinsic death pathway. However, a small portion of the Treg population is more sensitive to TCR stimulation, particularly weak stimulation, proliferates more vigorously than CD4(+) Tcon, and is resistant to activation-induced cell death. Treg proliferation is enhanced by IL-2 but is less dependent on CD28-mediated costimulation than that of Tcon. We demonstrate further that the surviving and proliferative Treg are ICOS(+) whereas the death-prone Treg are ICOS(-). Moreover, ICOS(+) Treg contain much stronger suppressive activity than that of ICOS(-) Treg. Our data indicate that massive death contributes to the anergic phenotype of Treg in vitro and suggest modulation of Treg survival as a therapeutic strategy for treatment of autoimmune diseases and cancer.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

February 15, 2012

Volume

188

Issue

4

Start / End Page

1698 / 1707

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • T-Lymphocytes, Regulatory
  • T-Lymphocyte Subsets
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Phenotype
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Interleukin-2
 

Citation

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MLA
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Chen, Y., Shen, S., Gorentla, B. K., Gao, J., & Zhong, X.-P. (2012). Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression. J Immunol, 188(4), 1698–1707. https://doi.org/10.4049/jimmunol.1102448
Chen, Yong, Shudan Shen, Balachandra K. Gorentla, Jimin Gao, and Xiao-Ping Zhong. “Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression.J Immunol 188, no. 4 (February 15, 2012): 1698–1707. https://doi.org/10.4049/jimmunol.1102448.
Chen Y, Shen S, Gorentla BK, Gao J, Zhong X-P. Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression. J Immunol. 2012 Feb 15;188(4):1698–707.
Chen, Yong, et al. “Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression.J Immunol, vol. 188, no. 4, Feb. 2012, pp. 1698–707. Pubmed, doi:10.4049/jimmunol.1102448.
Chen Y, Shen S, Gorentla BK, Gao J, Zhong X-P. Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression. J Immunol. 2012 Feb 15;188(4):1698–1707.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

February 15, 2012

Volume

188

Issue

4

Start / End Page

1698 / 1707

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • T-Lymphocytes, Regulatory
  • T-Lymphocyte Subsets
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Phenotype
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Interleukin-2