The role of FOXP3 + regulatory T cells in human autoimmune and inflammatory diseases

Summary CD4 + regulatory T cells (T reg ) expressing the forkhead box protein 3 (FOXP3) transcription factor (T regs ) are instrumental for the prevention of autoimmune diseases. There is increasing evidence that the human T regulatory population is highly heterogeneous in phenotype and function . Numerous studies conducted in human autoimmune diseases have shown that T reg cells are impaired either in their suppressive function, in number, or both. However, the contribution of the FOXP3 + T reg subpopulations to the development of autoimmunity has not been delineated in detail. Rare genetic disorders that involve deficits in T reg function can be studied to develop a global idea of the impact of partial or complete deficiency in a specific molecular mechanism involved in T reg function. In patients with reduced T reg numbers (but no functional deficiency), the expansion of autologous T reg cells could be a suitable therapeutic approach: either infusion of in‐vitro autologous expanded cells, infusion of interleukin (IL)‐2/anti‐IL‐2 complex, or both. T reg biology‐based therapies may not be suitable in patients with deficits of T reg function, unless their deficit can be corrected in vivo / in vitro . Finally, it is critical to consider the appropriate stage of autoimmune diseases at which administration of T reg cellular therapy can be most effective. We discuss conflicting data regarding whether T reg cells are more effectual at preventing the initiation of autoimmunity, ameliorating disease progression or curing autoimmunity itself.