title: Cytotoxic T-lymphocyte antigen-4 and programmed death-1 function as negative regulators of lymphocyte activation.
abstract: The B7 family of ligands and receptors plays a critical role in the modulation of immune responses. The B7/cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the more recently identified programmed death ligand/programmed death-1 (PD-L/PD-1) ligand/receptor pairs define pathways that function as rheostats of lymphocyte activation. Analysis of receptor and ligand expression patterns, as well as the phenotype of CTLA-4 or PD-1-deficient mice, strongly suggests that these pathways are nonredundant. Current data suggest that the B7/CTLA-4 pathway functions primarily to attenuate, limit, and/or terminate naïve T-cell activation in secondary lymphoid organs. The PD-L/PD-1 pathway, on the other hand, may primarily attenuate, limit, and/or terminate T-, B-, and myeloid cell activation/effector function at sites of inflammation in the periphery.
authors.affiliation: Wyeth Research, Cambridge, MA 02140, USA. bcarreno@wyeth.com
authors.forename: Laura L
authors.initials: LL
authors.lastname: Carter
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Carreno
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D006801:Humans; D008213:Lymphocyte Activation; D061026:Programmed Cell Death 1 Receptor; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor