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

J Immunol. 2002 Nov 15;169(10):5538-45. doi: 10.4049/jimmunol.169.10.5538.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • CHO Cells
  • Cell Line
  • 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

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • Cd274 protein, mouse
  • Ligands
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Pdcd1 protein, mouse
  • Pdcd1lg2 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor