T-cell activation is dependent on signals delivered through the antigen-specific T-cell receptor and accessory receptors on T-cells. Integration of signals through this family of costimulatory and inhibitory receptors and their ligands regulates the balance between T-cell activation, tolerance, and immunopathology. Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals and exert a vital and diverse range of immunoregulatory roles in T-cell activation, tolerance, and immune-mediated tissue damage. In this review, we revisit current understanding of the immunoregulatory functions of PD-1 and its ligands and their involvement in immune-mediated diseases.
Keywords: Alzheimer's disease, autoimmunity, costimulation, HIV infection, immune tolerance, multiple sclerosis, PD-1, PD-L1, T-cell activation, immune system, microbial pathogens, antigens, antigenic peptide/major histocompatibility complex, costimulatory signals, phenotype
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