Expression of Programmed Death 1 Ligands by Murine T Cells and APC

• Published in: The Journal of immunology (1950) Vol. 169; no. 10; pp. 5538 - 5545
• Main Authors: Yamazaki, Tomohide, Akiba, Hisaya, Iwai, Hideyuki, Matsuda, Hironori, Aoki, Mami, Tanno, Yuka, Shin, Tahiro, Tsuchiya, Haruo, Pardoll, Drew M, Okumura, Ko, Azuma, Miyuki, Yagita, Hideo
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-11-2002
• Subjects: Animals; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - metabolism; Antigen-Presenting Cells - cytology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens, Surface - biosynthesis; Antigens, Surface - metabolism; Apoptosis - immunology; Apoptosis Regulatory Proteins; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B7-1 Antigen - biosynthesis; B7-1 Antigen - genetics; B7-1 Antigen - immunology; B7-1 Antigen - metabolism; B7-H1 Antigen; Blood Proteins; Cell Line; CHO Cells; Cricetinae; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Leukemia L5178; Leukemia P388; Ligands; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Proteins - biosynthesis; Peptides; Programmed Cell Death 1 Ligand 2 Protein; Programmed Cell Death 1 Receptor; Rats; Rats, Sprague-Dawley; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transfection; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.10.5538

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.