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

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.