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A subclass of CD4 T cells referred to as Tregs are essential for peripheral tolerance and maintenance of immune homeostasis (Figure 2.2) [11]. Tregs mediate immune tolerance by functionally suppressing all activated CD4 T‐cell subsets and CD8 CTLs. Thus, reductions in the numbers or functional capacity of Tregs can facilitate autoimmunity and autoimmune diseases. Phenotypically, Tregs are CD4, CD25, forkhead box P3 (FoxP3) T cells. FoxP3 is the key regulator of Treg function, as shown by monogenic deficiency in FOXP3 that results in immunodysregulation, polyendocrinopathy and enteropathy X‐linked (IPEX) syndrome [1]. FoxP3‐deficient mice also develop autoimmune diseases, which can be prevented by adoptive transfer of CD4, CD25, FoxP3 Tregs. FoxP3 Tregs secrete immunoregulatory and immunosuppressive cytokines, including, IL‐9, IL‐35, IL‐10 and transforming growth factor (TGF)‐β. These cytokines immunosuppress activated CD4 and CD8 T cells and promote T‐cell anergy by downregulating APC expression of costimulatory CD80 and CD86. In addition, Treg upregulation of intracellular cyclic AMP directly inhibits cell proliferation and reduces production of IL‐2 required for T‐cell proliferation.