PD-1 and its ligands in tolerance and immunity.
Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune-mediated tissue damage. The PD-1:PD-L pathway also has been usurped by microorganisms and tumors to attenuate antimicrobial or tumor immunity and facilitate chronic infection and tumor survival. The identification of B7-1 as an additional binding partner for PD-L1, together with the discovery of an inhibitory bidirectional interaction between PD-L1 and B7-1, reveals new ways the B7:CD28 family regulates T cell activation and tolerance. In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential.
Keir
Mary E
ME
Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts 02115-5727, USA.
Butte
Manish J
MJ
Freeman
Gordon J
GJ
Sharpe
Arlene H
AH
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D018122:B7-1 Antigen / Q000502:physiology; D060890:B7-H1 Antigen; D006801:Humans; D007109:Immunity / Q000502:physiology*; D008024:Ligands; D018448:Models, Immunological; D061026:Programmed Cell Death 1 Receptor; D017634:Self Tolerance / Q000502:physiology*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D008024:Ligands; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor