title: Expression of programmed death 1 ligands by murine T cells and APC.
abstract: Programmed death 1 (PD-1) is a new member of the CD28/CTLA-4 family, which has been implicated in the maintenance of peripheral tolerance. Two ligands for PD-1, namely, B7-H1 (PD-L1) and B7-DC (PD-L2), have recently been identified as new members of the B7 family but their expression at the protein level remains largely unknown. To characterize the expression of B7-H1 and B7-DC, we newly generated an anti-mouse B7-H1 mAb (MIH6) and an anti-mouse B7-DC mAb (TY25). MIH6 and TY25 immunoprecipitated a single molecule of 43 and 42 kDa from the lysate of B7-H1 and B7-DC transfectants, respectively. Flow cytometric analysis revealed that B7-H1 was broadly expressed on the surface of mouse tumor cell lines while the expression of B7-DC was rather restricted. PD-1 was expressed on anti-CD3-stimulated T cells and anti-IgM plus anti-CD40-stimulated B cells at high levels but was undetectable on activated macrophages or DCs. B7-H1 was constitutively expressed on freshly isolated splenic T cells, B cells, macrophages, and dendritic cells (DCs), and up-regulated on T cells by anti-CD3 stimulation on macrophages by LPS, IFN-gamma, GM-CSF, or IL-4, and on DCs by IFN-gamma, GM-CSF, or IL-4. In contrast, B7-DC expression was only inducible on macrophages and DCs upon stimulation with IFN-gamma, GM-CSF, or IL-4. The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Iwai
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsuda
authors.forename: Mami
authors.initials: M
authors.lastname: Aoki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tanno
authors.forename: Tahiro
authors.initials: T
authors.lastname: Shin
authors.forename: Haruo
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen; D001798:Blood Proteins; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D007940:Leukemia L5178; D007941:Leukemia P388; D008024:Ligands; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C498919:Cd274 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor