Observations in Foxp3 gene-targeted mice further corroborated Treg cell paucity as the primary cause of early death and multi-organ autoimmunity in Foxp3-deficient mice (5) but also revealed the peripheral accumulation of Treg cell-like ‘wanna-be’ CD4+ T cells with self-reactive specificities (6–8) that contribute to the disease pathology (9, 10). This evidence concerns the gene CD4 and Autoimmunity.