Expression and function of the inducible costimulator ligand B7-H2 in human airway smooth muscle cells.
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.
Kajiwara
Keiichi
K
Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan.
Morishima
Hirotaka
H
Akiyama
Kazuo
K
Yanagihara
Yukiyoshi
Y
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D017252:CD3 Complex / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053278:OX40 Ligand / Q000096:biosynthesis / Q000235:genetics; D012137:Respiratory System / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019013:CD40 Antigens; C556692:ICOS protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D015850:Interleukin-6; D016209:Interleukin-8; D053278:OX40 Ligand