nTreg produced in thymus and released into periphery, prevent activation of destructive autoimmune responses. Absence of nTreg due to neonatal thymectomy (19), lack of IL-2, CD25, or FoxP3 (223) leads to widespread autoimmunity. Expression of CTLA4 is required for function of nTreg (224). These cells will control low level immune responses, and suppress at a ratio of 1:1 with more aggressive immune responses (58) including fully allogeneic responses (57, 59). They inhibit antigen presenting cells by direct contact and act in peripheral lymphoid tissues not at sites of inflammation. This evidence concerns the gene CTLA4 and Autoimmunity.