TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27Kip1

Jonathan Powell, Denis Bruniquel, Ronald H. Schwartz

Research output: Contribution to journalArticle

Abstract

We have proposed a model in which the prevention of anergy by costimulation is the result of IL-2-induced G1 to S phase cell cycle progression. Here we demonstrate that the reversal of anergy by exogenous IL-2 also occurs during this window of the cell cycle. Recently, it has been proposed that the cell cycle inhibitor p27Kip1 is an anergic factor. In contrast, our data demonstrate that during the induction, maintenance and rechallenge phases of anergy, p27Kip1 levels do not correlate with the anergic phenotype. Although p27Kip1 levels were down-regulated by IL-2 during the G1 to S phase transition, the amount of IL-2 required to produce this effect was far lower than that required to prevent the induction of anergy. Furthermore, T cell lines from p27Kip1 knockout mice were anergized as well as T cells from mice that were heterozygous for p27Kip1. Interestingly, the forced overexpression of p27Kip1 was able to decrease IL-2 promoter-induced transcription, suggesting that the cell cycle machinery may be involved in T cell activation; however, physiological levels of p27Kip1 did not prevent IL-2 transcription. Overall, our data serve to disassociate the ability of IL-2 to down-regulate p27Kip1 and its ability to prevent or reverse anergy.

Original languageEnglish (US)
Pages (from-to)3737-3746
Number of pages10
JournalEuropean Journal of Immunology
Volume31
Issue number12
DOIs
StatePublished - 2001

Fingerprint

Interleukin-2
Cell Cycle
T-Lymphocytes
S Phase
Phase Transition
Knockout Mice
Down-Regulation
Maintenance
Phenotype
Cell Line

Keywords

  • Anergy
  • Cell cycle
  • IL-2
  • p27
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology

Cite this

TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27Kip1. / Powell, Jonathan; Bruniquel, Denis; Schwartz, Ronald H.

In: European Journal of Immunology, Vol. 31, No. 12, 2001, p. 3737-3746.

Research output: Contribution to journalArticle

@article{8e6ca2c4b3cc47d183e520481c3aae79,
title = "TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27Kip1",
abstract = "We have proposed a model in which the prevention of anergy by costimulation is the result of IL-2-induced G1 to S phase cell cycle progression. Here we demonstrate that the reversal of anergy by exogenous IL-2 also occurs during this window of the cell cycle. Recently, it has been proposed that the cell cycle inhibitor p27Kip1 is an anergic factor. In contrast, our data demonstrate that during the induction, maintenance and rechallenge phases of anergy, p27Kip1 levels do not correlate with the anergic phenotype. Although p27Kip1 levels were down-regulated by IL-2 during the G1 to S phase transition, the amount of IL-2 required to produce this effect was far lower than that required to prevent the induction of anergy. Furthermore, T cell lines from p27Kip1 knockout mice were anergized as well as T cells from mice that were heterozygous for p27Kip1. Interestingly, the forced overexpression of p27Kip1 was able to decrease IL-2 promoter-induced transcription, suggesting that the cell cycle machinery may be involved in T cell activation; however, physiological levels of p27Kip1 did not prevent IL-2 transcription. Overall, our data serve to disassociate the ability of IL-2 to down-regulate p27Kip1 and its ability to prevent or reverse anergy.",
keywords = "Anergy, Cell cycle, IL-2, p27, T lymphocyte",
author = "Jonathan Powell and Denis Bruniquel and Schwartz, {Ronald H.}",
year = "2001",
doi = "10.1002/1521-4141(200112)31:12<3737::AID-IMMU3737>3.0.CO;2-G",
language = "English (US)",
volume = "31",
pages = "3737--3746",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "12",

}

TY - JOUR

T1 - TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27Kip1

AU - Powell, Jonathan

AU - Bruniquel, Denis

AU - Schwartz, Ronald H.

PY - 2001

Y1 - 2001

N2 - We have proposed a model in which the prevention of anergy by costimulation is the result of IL-2-induced G1 to S phase cell cycle progression. Here we demonstrate that the reversal of anergy by exogenous IL-2 also occurs during this window of the cell cycle. Recently, it has been proposed that the cell cycle inhibitor p27Kip1 is an anergic factor. In contrast, our data demonstrate that during the induction, maintenance and rechallenge phases of anergy, p27Kip1 levels do not correlate with the anergic phenotype. Although p27Kip1 levels were down-regulated by IL-2 during the G1 to S phase transition, the amount of IL-2 required to produce this effect was far lower than that required to prevent the induction of anergy. Furthermore, T cell lines from p27Kip1 knockout mice were anergized as well as T cells from mice that were heterozygous for p27Kip1. Interestingly, the forced overexpression of p27Kip1 was able to decrease IL-2 promoter-induced transcription, suggesting that the cell cycle machinery may be involved in T cell activation; however, physiological levels of p27Kip1 did not prevent IL-2 transcription. Overall, our data serve to disassociate the ability of IL-2 to down-regulate p27Kip1 and its ability to prevent or reverse anergy.

AB - We have proposed a model in which the prevention of anergy by costimulation is the result of IL-2-induced G1 to S phase cell cycle progression. Here we demonstrate that the reversal of anergy by exogenous IL-2 also occurs during this window of the cell cycle. Recently, it has been proposed that the cell cycle inhibitor p27Kip1 is an anergic factor. In contrast, our data demonstrate that during the induction, maintenance and rechallenge phases of anergy, p27Kip1 levels do not correlate with the anergic phenotype. Although p27Kip1 levels were down-regulated by IL-2 during the G1 to S phase transition, the amount of IL-2 required to produce this effect was far lower than that required to prevent the induction of anergy. Furthermore, T cell lines from p27Kip1 knockout mice were anergized as well as T cells from mice that were heterozygous for p27Kip1. Interestingly, the forced overexpression of p27Kip1 was able to decrease IL-2 promoter-induced transcription, suggesting that the cell cycle machinery may be involved in T cell activation; however, physiological levels of p27Kip1 did not prevent IL-2 transcription. Overall, our data serve to disassociate the ability of IL-2 to down-regulate p27Kip1 and its ability to prevent or reverse anergy.

KW - Anergy

KW - Cell cycle

KW - IL-2

KW - p27

KW - T lymphocyte

UR - http://www.scopus.com/inward/record.url?scp=0035660104&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035660104&partnerID=8YFLogxK

U2 - 10.1002/1521-4141(200112)31:12<3737::AID-IMMU3737>3.0.CO;2-G

DO - 10.1002/1521-4141(200112)31:12<3737::AID-IMMU3737>3.0.CO;2-G

M3 - Article

C2 - 11745394

AN - SCOPUS:0035660104

VL - 31

SP - 3737

EP - 3746

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 12

ER -