Therapeutic opportunities for manipulating T(Reg) cells in autoimmunity and cancer.

Forkhead box P3 (FOXP3)-expressing regulatory T (T(Reg)) cells have a pivotal role in the regulation of immune responses and in the maintenance of immunological self-tolerance. These cells have emerged as attractive targets for strategies that allow the steering of immune responses in desired directions - arming the immune system to destroy infected cells and cancer cells or downregulating it to limit tissue destruction in autoimmunity. Efforts to understand the generation, activation and function of T(Reg) cells should permit the development of therapeutics for reprogramming the immune system. In this Review, we discuss insights into the generation of T(Reg) cells, their involvement in disease and the molecular basis of the dominant tolerance exerted by FOXP3(+) T(Reg) cells that could permit their safe and specific manipulation in humans.