title: PD-1 inhibits antiviral immunity at the effector phase in the liver.
abstract: Unlike naive T cells, effector T cells can be activated by either T cell receptor signal or costimulatory signal alone and therefore the absence of costimulatory molecules on tissue cells cannot explain the tolerance mechanism at the effector phase. Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues. Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1. The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.
authors.affiliation: Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwai
authors.forename: Seigo
authors.initials: S
authors.lastname: Terawaki
authors.forename: Masaya
authors.initials: M
authors.lastname: Ikegawa
authors.forename: Taku
authors.initials: T
authors.lastname: Okazaki
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000737:chemistry; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C498919:Cd274 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma