How regulatory T cells work

Regulatory T cells (TReg cells) have a central role in immune regulation, but how do they work? In this Review, our current understanding of the suppressive mechanisms used by TReg cells is described and the relative contribution of these mechanisms to TReg-cell function is discussed. Regulatory T (TReg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. However, they also limit beneficial responses by suppressing sterilizing immunity and limiting antitumour immunity. Given that TReg cells can have both beneficial and deleterious effects, there is considerable interest in determining their mechanisms of action. In this Review, we describe the basic mechanisms used by TReg cells to mediate suppression and discuss whether one or many of these mechanisms are likely to be crucial for TReg-cell function. In addition, we propose the hypothesis that effector T cells may not be 'innocent' parties in this suppressive process and might in fact potentiate TReg-cell function.