An essential role for the IL-2 receptor in Treg cell function

The cytokine receptor IL-2R is essential for the development of T reg cells; therefore, it has been difficult to separate this from its role in the suppressive function of T reg cells. Rudensky and colleagues use various genetic systems to show that capture of IL-2 by IL-2R is important for suppression of CD8 + T cells but not that of CD4 + T cells. Regulatory T cells (T reg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by T reg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the T reg cell lineage–specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of T reg cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4 + T cells but was important for limiting the activation of CD8 + T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of T reg cells separable from signaling via the T cell antigen receptor.