CTLA4 and Autoimmunity: Def6 deficiency in murine autoimmunity appears to depend on the genetic background and/or the employed model of autoimmune disease.63,64 The recent discovery of human DEF6 deficiency, which manifests as systemic autoimmunity and lymphoproliferation, revealed the homeostatic role of DEF6 in the human immune system.65 Similar to LRBA deficiency, DEF6 deficiency causes a CTLA-4 trafficking defect, resulting in reduced stimulation-induced CTLA-4 expression by Tregs.