Vascular endothelial cells provide T cells with costimulatory signals via the OX40/gp34 system

J Leukoc Biol. 2000 Jul;68(1):111-8.

Abstract

We investigated whether gp34, the ligand of OX40, expressed on EC is involved in costimulation of T cells. Normal CD4+ T cells were stimulated with anti-CD3-coated beads, phytohemagglutinin (PHA), or concanavalin A (Con A) in the presence or absence of irradiated human umbilical vein endothelial cells (HUVEC). Stimulation of T cells with each of these mitogens results in significant T-cell proliferation only when HUVEC were present, and this proliferation was inhibited markedly by anti-OX40 or anti-gp34 monoclonal antibody (mAb). T cells cultured with HUVEC produced more interleukin (IL)-2 than those cultured without HUVEC. The addition of anti-IL-2R alpha chain and anti-IL-2R beta chain mAbs abolished the costimulatory effects of HUVEC. Thus, the augmentation of T-cell proliferation appears to be attributable to increased IL-2 production. These results suggest that gp34 expressed on HUVEC plays a role in potentiation of T-cell immune response by providing OX40+ T cells with costimulatory signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antigens, Surface
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Adhesion Molecules / physiology
  • Cell Division / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / radiation effects
  • Formaldehyde / pharmacology
  • HLA-DR Antigens / biosynthesis
  • HLA-DR Antigens / genetics
  • Humans
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation / physiology*
  • Membrane Proteins
  • Polymers / pharmacology
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / genetics
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / physiology*
  • Umbilical Veins

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Cell Adhesion Molecules
  • HLA-DR Antigens
  • Interleukin-2
  • Membrane Proteins
  • Polymers
  • Receptors, Interleukin-2
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • TNFRSF4 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factor-alpha
  • Formaldehyde
  • paraform