Expression and function of the inducible costimulator ligand B7-H2 in human airway smooth muscle cells

Allergol Int. 2009 Dec;58(4):573-83. doi: 10.2332/allergolint.09-OA-0113. Epub 2009 Sep 25.


Background: B7-H2 is a ligand for the inducible costimulator (ICOS). The aim of this study was to examine the expression and function of B7-H2 in human airway smooth muscle (ASM) cells and compare them with those of CD40 or OX40 ligand (OX40L).

Methods: Expression of B7-H2, CD40 and OX40L in ASM cells and their respective counterparts in T cells was analyzed by RT-PCR or flow cytometry. The modulating effect of polyinosinic-polycytidylic acid (poly I:C) on expression of B7-H2, CD40 and OX40L was also examined. The function of these three molecules was evaluated by virtue of adhesion of anti-CD3-activated T cells, IL-6 and IL-8 production and DNA synthesis.

Results: ASM cells constitutively expressed B7-H2, CD40 and OX40L that mediated adhesion of activated T cells expressing ICOS, CD40L and OX40. ASM cells responded to poly I:C with upregulated expression of B7-H2, CD40 and OX40L and displayed enhanced adhesion of activated T cells. Functional analysis performed on untreated ASM cells showed that engagement of B7-H2 with ICOS-Ig clearly induced DNA synthesis, whereas that of CD40 or OX40L with trimeric CD40L or OX40-Ig greatly increased IL-6 and IL-8 production. These responses were enhanced in poly I:C-treated ASM cells.

Conclusions: The data demonstrate that ASM cells express functionally active B7-H2, CD40 and OX40L and suggest that B7-H2-dependent signaling may play an active role in a proliferative response rather than in cytokine and chemokine production. In addition, the modulation of B7-H2, CD40 and OX40L expression and function by poly I:C may have important implications for the function of virus-infected ASM cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • CD3 Complex / immunology
  • CD40 Antigens / biosynthesis
  • CD40 Antigens / genetics
  • Cell Adhesion / immunology
  • Cell Separation
  • Cells, Cultured
  • Flow Cytometry
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Myocytes, Smooth Muscle / immunology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • OX40 Ligand / biosynthesis
  • OX40 Ligand / genetics
  • Respiratory System / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD40 Antigens
  • ICOS protein, human
  • ICOSLG protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-6
  • Interleukin-8
  • OX40 Ligand