PDCD1 and autoimmune disease: Consistent with their roles in the physiological regulation of cellular immune responses, CTLA-4−/− and PD-1−/− mice develop spontaneous autoimmune diseases; CTLA-4−/− mice die 2–3 weeks after birth from systemic lymphoproliferation [9], [10] while PD-1−/− mice develop lupus-like glomerulonephritis and destructive arthritis [11], [12].