Cutting Edge: Mechanisms of IL-2–Dependent Maintenance of Functional Regulatory T Cells

Abstract

IL-2 controls the survival of regulatory T cells (Tregs), but it is unclear whether IL-2 also directly affects Treg suppressive capacity in vivo. We have found that eliminating Bim-dependent apoptosis in IL-2– and CD25-deficient mice restored Treg numbers but failed to cure their lethal autoimmune disease, demonstrating that IL-2–dependent survival and suppressive activity can be uncoupled in Tregs. Treatment with IL-2–anti–IL-2–Ab complexes enhanced the numbers and suppressive capacity of IL-2–deprived Tregs with striking increases in CD25, CTLA-4, and CD39/CD73 expression. Although cytokine treatment induced these suppressive mechanisms in both IL-2−/− and IL-2−/−Bim−/− mice, it only reversed autoimmune disease in the latter. Our results suggest that successful IL-2 therapy of established autoimmune diseases will require a threshold quantity of Tregs present at the start of treatment and show that the suppressive capacity of Tregs critically depends on IL-2 even when Treg survival is independent of this cytokine.