Interleukin-2 is essential for CD4+CD25+ regulatory T cell function.

Abstract:

:Constitutive expression of CD25, the IL-2 receptor alpha-chain, defines a distinct population of CD4+ T cells (Treg) with suppressive activity in vitro and in vivo. IL-2 has been implicated in the generation and maintenance of Treg, however, a functional contribution of the IL-2 receptor during suppression is thus far unknown. We show that IL-2 is required for Treg function in vitro, since suppression is completely abrogated by selective blocking of the IL-2 receptor on Treg during co-culture with responder T cells. We demonstrate that Treg, which do not produce IL-2, compete for IL-2 secreted by responder T cells. In accordance with the idea of competition being part of the suppressive mechanism, in vitro neutralization of IL-2 mimics all effects of Treg. Conversely, recombinant IL-2 abrogates inhibition of IL-2 production in responder T cells, the hallmark of Treg suppression. Finally, activation in the presence of IL-2 primes Treg to produce IL-10 upon secondary stimulation, indicating that IL-2 uptake is also required to induce additional suppressive factors that might be more relevant for suppression in vivo. We propose the parakrine uptake of soluble mediators as a flexible mechanism to adapt Treg activity to the strength of the responder T cell reaction.

journal_name

Eur J Immunol

authors

de la Rosa M,Rutz S,Dorninger H,Scheffold A

doi

10.1002/eji.200425274

keywords:

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

2480-8

issue

9

eissn

0014-2980

issn

1521-4141

journal_volume

34

pub_type

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