title: B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance.
abstract: T-cell tolerance is the central program that prevents harmful immune responses against self-antigens, in which inhibitory PD-1 signal given by B7-H1 interaction plays an important role. Recent studies demonstrated that B7-H1 binds CD80 besides PD-1, and B7-H1/CD80 interaction also delivers inhibitory signals in T cells. However, a role of B7-H1/CD80 signals in regulation of T-cell tolerance has yet to be explored. We report here that attenuation of B7-H1/CD80 signals by treatment with anti-B7-H1 monoclonal antibody, which specifically blocks B7-H1/CD80 but not B7-H1/PD-1, enhanced T-cell expansion and prevented T-cell anergy induction. In addition, B7-H1/CD80 blockade restored Ag responsiveness in the previously anergized T cells. Experiments using B7-H1 or CD80-deficient T cells indicated that an inhibitory signal through CD80, but not B7-H1, on T cells is responsible in part for these effects. Consistently, CD80 expression was detected on anergic T cells and further up-regulated when they were re-exposed to the antigen (Ag). Finally, blockade of B7-H1/CD80 interaction prevented oral tolerance induction and restored T-cell responsiveness to Ag previously tolerized by oral administration. Taken together, our findings demonstrate that the B7-H1/CD80 pathway is a crucial regulator in the induction and maintenance of T-cell tolerance.
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, USA.
authors.forename: Jang-June
authors.initials: JJ
authors.lastname: Park
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Omiya
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Sakoda
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kuramasu
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Augustine
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Tsushima
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Narazaki
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Anand
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Liu
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology; D001324:Autoantigens / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D015153:Blotting, Western; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000502:physiology*; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D001324:Autoantigens; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010446:Peptide Fragments; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin
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