CTLA4 and autoimmune disease: Freed CTLA-4 recycles back to the cell surface, where it is required for Treg to protect mice against autoimmune diseases.4 The recycling requires CTLA-4-LRBA interactions as it is abrogated by a mutation of CTLA-4 that disrupts the interaction.36 The significance of intact CTLA-4 recycling in protecting against irAE is demonstrated by the fact that Primaquine, which blocks CTLA-4 recycling, confers irAE activity to HL12.