title: Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells.
abstract: Expression of the PD-1 receptor on T cells has been shown to provide an important inhibitory signal that down-modulates peripheral effector responses in normal tissues and tumors. Furthermore, PD-1 up-regulation on chronically activated T cells can maintain them in a partially reversible inactive state. The function of PD-1 in the very early stages of T-cell response to antigen in vivo has not been fully explored. In this study, we evaluate the role of PD-1 and its 2 B7 family ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), in early fate decisions of CD8 T cells. We show that CD8 T cells specific for influenza hemagglutinin (HA) expressed as a self-antigen become functionally tolerized and express high levels of surface PD-1 by the time of their first cell division. Blockade of PD-1 or B7-H1, but not B7-DC, at the time of self-antigen encounter mitigates tolerance induction and results in CD8 T-cell differentiation into functional cytolytic T lymphocytes (CTLs). These findings demonstrate that, in addition to modulating effector functions in the periphery, B7-H1:PD-1 interactions regulate early T-cell-fate decisions.
authors: Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
authors: Monica V
authors: MV
authors: Goldberg
authors: Charles H
authors: CH
authors: Maris
authors: Edward L
authors: EL
authors: Hipkiss
authors: Andrew S
authors: AS
authors: Flies
authors: Lijie
authors: L
authors: Zhen
authors: Rubin M
authors: RM
authors: Tuder
authors: Joseph F
authors: JF
authors: Grosso
authors: Timothy J
authors: TJ
authors: Harris
authors: Derese
authors: D
authors: Getnet
authors: Katharine A
authors: KA
authors: Whartenby
authors: Dirk G
authors: DG
authors: Brockstedt
authors: Thomas W
authors: TW
authors: Dubensky
authors: Lieping
authors: L
authors: Chen
authors: Drew M
authors: DM
authors: Pardoll
authors: Charles G
authors: CG
authors: Drake
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D001324:Autoantigens; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010455:Peptides / Q000502:physiology*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D011485:Protein Binding; D017634:Self Tolerance; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D001324:Autoantigens; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor