Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL‐)two to tango

Abstract

Although CD4⁺CD25⁺ regulatory T cells (Treg) represent a well‐characterized population of T cells with in vitro and in vivo suppressive capacity, the basic mechanisms of suppression are still not understood. The constitutive expression of the high‐affinity receptor for IL‐2 has raised the question about the role of IL‐2 in Treg function. Here, we review recent data indicating that IL‐2 is not only necessary for the homeostasis of Treg but is also critical for the activation of Treg function. Since Treg do not produce IL‐2 by themselves, their capacity to utilize IL‐2 secreted by other T cells appears to be an essential component of Treg biology. This indicates that Treg suppressive activity is controlled by interaction with activated target cells via the soluble mediator IL‐2. In Treg, IL‐2 has been identified as a potent inducer of the immunosuppressive cytokine IL‐10, an important mediator of Treg suppression in vivo. The efficient capture of IL‐2 by Treg may, under conditions of limited IL‐2 supply, cause IL‐2 deprivation of responder T cells. This competition can explain some of the currently discussed discrepancies between in vivo and in vitro activity of Treg.