CTLA4 and Autoimmunity: Consequently, defects in CTLA-4 protein expression or trafficking pathways result in immune dysregulation (3, 4), as evidenced by CTLA-4 haploinsufficiency in humans and Ctla4−/− mice—both of which show decreased frequency of Tregs, multiorgan lymphocytic infiltration, and autoimmunity (4, 5).