Mechanisms of central and peripheral T-cell tolerance: An update

To function properly, the immune system must deal with randomly generated immune receptors that by chance can recognize self-antigens. Most solutions to this self-tolerance problem are cell intrinsic and involve the deletion or inactivation of autoreactive cells. This review will present an update of the concepts of an extrinsic form of dominant tolerance mediated by regulatory T cells. Throughout, new tools to identify and manipulate these regulatory T cells will be discussed. These basics should enable us to unlock their clinical potential to specifically suppress immune responses in autoimmunity and transplantation and to antagonize regulatory T cells where a boost of immunity is required, e.g. in infectious diseases and anti-tumor immune responses.