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

Eur J Immunol. 2004 Sep;34(9):2480-8. doi: 10.1002/eji.200425274.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / physiology
  • Coculture Techniques
  • Interleukin-10 / biosynthesis
  • Interleukin-2 / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Interleukin-2 / analysis*
  • T-Lymphocytes, Regulatory / physiology


  • Interleukin-2
  • Receptors, Interleukin-2
  • Interleukin-10