| Regulatory T cells play an important non-redundant role in the maintenance of peripheral tolerance in mice and humans. Signals required for their development, homeostasis and function are largely unknown. Recent studies point to a critical role of IL-2 signaling in Treg biology. Here, we show that IL-2 receptor signals are mainly required for the induction of FoxP3 expression. Transgenic expression of a FoxP3 transgene could compensate for the function of IL-2 receptor signaling in Treg development, maintenance and function. We further determined that the constitutive activation of the transcription factor Stat5, which is downstream of IL-2 signaling, enhances Treg function in vitro and in vivo. In contrast, an increase in Stat5 activation negatively affected CD4 effector T cells and reduced their ability to induce graft-versus-host disease. Together, these data suggest that Stat5 has a dual role in immune regulation by increasing regulatory T cell and limiting effector T cell functions. Regulatory T cells comprise a small fraction of T cells in the body. In vitro activation and expansion protocols have been developed to increase their numbers and function for clinical purposes. We show here, that such expansion protocols can support outgrowth of non-regulatory T cells with potent suppressor function in vitro. |
