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

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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Duré M,Macian F

doi

10.1016/j.molimm.2008.09.029

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

999-1006

issue

5

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(08)00695-0

journal_volume

46

pub_type

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