An essential role for IL-2 receptor in regulatory T cell function

Regulatory T (T(reg)) cells, expressing abundant amounts of the IL-2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature implied a key role for a simple network based on IL-2 consumption 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, confounding experimental efforts to understand the role of IL-2R expression and signaling in T(reg) suppressor function. Using genetic gain and loss of function approaches, we demonstrate that IL-2 capture is dispensable for control of CD4(+) T cells, but is important for limiting CD8(+) T cell activation, and that IL-2R dependent STAT5 transcription factor activation plays an essential role in T(reg) cell suppressor function separable from T cell receptor signaling.