CD4 and autoimmune disease: They are indispensable for the maintenance of immunological self-tolerance.1–3 For example, removal of CD25+CD4+ Treg cells from the immune system results in spontaneous development of various autoimmune diseases, such as autoimmune thyroiditis and type 1 diabetes, in otherwise normal rodents.4 Mutations of the FOXP3 gene cause similar autoimmune diseases in humans5 and systemic autoimmunity in mice.5–7 Mutations of the IL2RA and CTLA4 genes also produce autoimmune/inflammatory diseases in humans and mice, at least in part, by impairing nTreg cell function.