Expression and Regulation of the PD-L1 Immunoinhibitory Molecule on Microvascular Endothelial Cells

Microcirculation. 2002 Apr;9(2):133-45. doi: 10.1038/sj/mn/7800123.

Abstract

Objective: To evaluate the expression and regulation of a novel B7-like protein, PD-L1, the ligand for the immunoinhibitory receptor PD-1 expressed on activated T-cells, on microvascular endothelial cells (ECs)

Methods: PD-L1 expression on ECs in vitro and in vivo was quantified by using a dual radiolabeled antibody technique after treatment with interferons (IFN) and IL-12, respectively. Changes in the level of PD-L1 mRNA were determined by using RT-PCR.

Results: PD-L1 was observed to be present on ECs under basal conditions. Treatment of ECs with IFN-alpha, -beta and -gamma, but not LPS, was observed to induce elevations in the mRNA and surface expression of PD-L1 on ECs. By using a dual radiolabeled monoclonal antibody (mAb) technique, PD-L1 expression in various tissues of control and IL-12 challenged wild-type and IFN-gamma-deficient mice was measured. A significant increase in PD-L1 expression was observed in tissues at 24 hours after IL-12-challenge, with peak levels of PD-L1 occurring 72 hours after IL-12 challenge. IL-12 was not effective at inducing PD-L1 expression in tissues of IFN-gamma-deficient mice.

Conclusions: These data show the expression of a novel B7-like molecule on murine ECs that is mediated by IFN-alpha, -beta, and -gamma, and suggest a potential pathway by which ECs may modulate T-cell function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B7-1 Antigen*
  • B7-H1 Antigen
  • Blood Proteins / genetics*
  • Blood Proteins / immunology
  • Blood Proteins / metabolism*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / metabolism
  • Gene Expression Regulation / drug effects
  • In Vitro Techniques
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / pharmacology
  • Interleukin-12 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microcirculation / drug effects
  • Microcirculation / immunology
  • Microcirculation / metabolism
  • Peptides / genetics*
  • Peptides / immunology
  • Peptides / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins
  • T-Lymphocytes / immunology

Substances

  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • Cd274 protein, mouse
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Peptides
  • RNA, Messenger
  • Recombinant Proteins
  • Interleukin-12
  • Interferon-gamma