IL-2 signaling prevents T cell anergy by inhibiting the expression of anergy-inducing genes

Myrianne Duré, Fernando Macian

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

T cell responses are determined by the environment in which antigen is encountered. In the absence of proper costimulation, anergizing stimuli induce the activation of a specific program of gene expression. Proteins encoded by these genes impose a state of functional unresponsiveness in anergic T cells through the activation of different mechanisms that include dampening of the T cell receptor signaling and direct inhibition of cytokine expression. Anergy can be reversed by stimulating T cells in the presence of interleukin (IL-)2. Signaling through the IL-2 receptor has been shown to activate mTOR, which plays an important role in the integration of signals that determine the fate of T cells. The mechanisms underlying the IL-2-dependent regulation of T cell tolerance are still not fully elucidated. In this study we show that IL-2 receptor signaling mediated through JAK3 and mTOR inhibits the expression of anergy-inducing genes independently of any effect on cell cycle progression. Interestingly, we also show that this effect is likely due to changes on the levels of AP-1 activation induced by IL-2 receptor signaling in T cells. Our data identifies a mechanism that can explain how IL-2 may prevent or reverse the establishment of anergy in T cells and, therefore, helps to understand how the cytokine environment can be determinant to shape the outcome of T cell responses - tolerance or activation - when antigen is encountered.

Original languageEnglish (US)
Pages (from-to)999-1006
Number of pages8
JournalMolecular Immunology
Volume46
Issue number5
DOIs
StatePublished - Feb 1 2009

Keywords

  • Anergy
  • Interleukin 2
  • NFAT
  • T cell
  • mTOR

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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