Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets.

Regulatory T cells (Tregs) require IL-2 for survival in the periphery, yet how IL-2 shapes Treg heterogeneity remains poorly defined. Here we show that inhibition of IL-2R signaling in post-thymic Tregs leads to a preferential early loss of circulating Tregs (cTregs). Gene expression of cTregs was more dependent on IL-2R signaling than effector Tregs (eTregs).

Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer.

Interleukin-2 (IL-2) is a critical cytokine for T cell peripheral tolerance and immunity. Here, we review how IL-2 interaction with the high-affinity IL-2 receptor (IL-2R) supports the development and homeostasis of regulatory T cells and contributes to the differentiation of helper, cytotoxic, and memory T cells. A critical element for each T cell population is the expression of CD25 (Il2rα), which heightens the receptor affinity for IL-2.