Cutting Edge: A Regulatory T Cell-Dependent Novel Function of CD25 (IL-2Rα) Controlling Memory CD8+ T Cell Homeostasis

Abstract

A massive systemic expansion of CD8+ memory T (TM) cells and a remarkable increase in circulating IL-2 were observed only in IL-2Rα (CD25) knockout (KO) mice but not in IL-2 KO and scurfy mice, although all three mutants lack regulatory T (Treg) cells. However, both phenotypes were suppressed by the transfer of Treg cells. The data presented indicate that Treg cell deficiency drives naive T cells to TM cells. The lack of high-affinity IL-2R in IL-2Rα KO mice increases circulating IL-2 that is then preferentially used by CD8+ TM cells through its abundant low-affinity IL-2R, resulting in systemic CD8+ TM cell dominance. Our study demonstrates the critical control of CD8+ TM cell homeostasis by a Treg cell-dependent novel function of CD25 and resolves its mechanism of action.