CD4 and systemic lupus erythematosus: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with the breakdown in self-tolerance and the generation of autoantibodies.1–3 Double-negative (CD3+CD4-CD8-, DN) T cells, a unique subset of T cells lacking CD4 and CD8 co-receptors, play a significant role in the pathogenesis of autoimmune diseases, such as SLE.4 During SLE progress, DN T cells invade into multiple organs, contributing to the loss of tolerance.