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Depletion of regulatory T (T_Reg) cells in otherwise healthy individuals leads to multi-organ autoimmune disease and inflammation. This indicates that in a normal immune system, there are self-specific effector T cells that are ready to attack normal tissue if they are not restrained by T_Reg cells. The data imply that there is a balance between effector T cells and T_Reg cells in health and suggest a therapeutic potential of T_Reg cells in diseases in which this balance is altered. Proof-of-concept clinical trials, now supported by robust mechanistic studies, have shown that low-dose interleukin-2 specifically expands and activates T_Reg cell populations and thus can control autoimmune diseases and inflammation.