Interleukin-2 is essential for CD4+CD25+ regulatory T cell function.
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.
Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany.
Maurus
M
de la Rosa
Sascha
S
Rutz
Heike
H
Dorninger
Alexander
A
Scheffold
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D018920:Coculture Techniques; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D016753:Interleukin-10