PD-1 and autoimmunity.

An initiating T cell response requires both costimulatory signaling and T cell receptor/MHC binding. The immune system balances positive and negative costimulatory signal pathways to activate and deactivate T cells. This review focuses primarily on PD-1 and its ligands, which form a crucial inhibitory costimulatory pathway for maintaining peripheral tolerance, and their contribution to autoimmunity. Since 1992, when PD-1 was isolated, many studies have described the physiological roles of PD-1 signaling, reported relationships between Pdcd-1 gene polymorphism and autoimmune diseases, and applied PD-1/PD-1 ligand modulation to clinical trials. This review summarizes recent advances and future therapeutic applications of PD-1 and its ligands to autoimmune diseases.