IL-2 Family of Cytokines in T Regulatory Cell Development and Homeostasis

Abstract

Interleukin 2 (IL-2) induces an essential signal for T regulatory (Treg) cells. Without a functional IL-2R, only immature CD4(+) Foxp3(low) CD25(neg) T cells develop, and these cells fail to suppress autoreactive T cells in the periphery. IL-2 functions during Treg cell development by upregulating Foxp3 and CD25 and by increasing the number of thymic Treg cells. Upon exiting the thymus during neonatal life, IL-2 is responsible for rapid amplification of the number of Treg cells in peripheral lymph nodes to insure suppression of autoreactive T cells that escape negative selection, thereby maintaining tolerance. The homeostasis of Treg cells in mature immunocompetent mice also depends on IL-2. However, there is an alternative mechanism for Treg cells homeostasis that may represent a minor IL-2-independent pathway or the consequence of weak and very transient IL-2R signaling. Thus, IL-2 provides importance signals for Treg cell development and for their homeostasis in peripheral immune tissues.