CD4 and Autoimmunity: The PD-1:PD-L1 pathway is known to eliminate autoreactive T cells and protect against autoimmunity.45 PD-1−/− mice develop lupus-like disease including glomerulonephritis.46 Additionally, CD274/PD-L1 has been shown to play an important role in T regulatory cell generation from naive CD4 T cells.47 In human SLE, CD274/PD-L1 is suppressed in flare but returns when disease is in remission.29 This suggests that suppression of CD274/PD-L1 as seen in NR may lead to unregulated autoreactive T cell activation and defective tolerance compared with CR.