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

• Published in: European Journal of Immunology 2004-01, Vol.34 (9), p.2480-2488
• Main Authors: De la Rosa, Maurus, Rutz, Sascha, Dorninger, Heike, Scheffold, Alexander
• Format: Article
• Language: English
• ISSN: 0014-2980; 1365-2567
• DOI: 10.1002/eji.200425274

Constitutive expression of CD25, the IL-2 receptor alpha -chain, defines a distinct population of CD4 super(+) 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.