First Author | de la Rosa M | Year | 2004 |
Journal | Eur J Immunol | Volume | 34 |
Issue | 9 | Pages | 2480-8 |
PubMed ID | 15307180 | Mgi Jnum | J:91773 |
Mgi Id | MGI:3050725 | Doi | 10.1002/eji.200425274 |
Citation | De La Rosa M, et al. (2004) Interleukin-2 is essential for CD4(+)CD25(+) regulatory T cell function. Eur J Immunol 34(9):2480-8 |
abstractText | 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. |