Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma

被引:117
作者
Hoshino, A
Tanaka, Y
Akiba, H
Asakura, Y
Mita, Y
Sakurai, T
Takaoka, A
Nakaike, S
Ishii, N
Sugamura, K
Yagita, H
Okumura, K
机构
[1] Taisho Pharmaceut Co Ltd, Med Res Lab, Omiya, Saitama 3308530, Japan
[2] Tohoku Univ, Grad Sch Med, Dept Microbiol & Immunol, Sendai, Miyagi 980, Japan
[3] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan
关键词
allergy; inflammation; costimulation; cell surface molecule;
D O I
10.1002/eji.200323455
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Bronchial asthma is characterized by massive infiltration of eosinophils and airway hyperreactivity (AHR), which are caused by overproduction of Th2 cytokines (IL-4, IL-5, and IL-13) by allergen-specific T cells. We recently demonstrated a critical contribution of OX40 ligand (OX40L) to the development of Th2-mediated experimental leishmaniasis. In this study, we have examined the role of OX40L in the development of Th2-mediated pulmonary inflammation by utilizing OX40L-deficient mice and a neutralizing anti-OX40L mAb in a murine model of asthma. Sensitization and airway challenge with ovalbumin in wild-type BALB/c mice induced a typical allergic asthma characterized by AHR, accumulation of eosinophils, increased mucus production, and high levels of Th2 cytokines in the lung. All these asthmatic responses were not induced in OX40L-deficient BALB/c mice. Administration of neutralizing anti-OX40L mAb in wild-type BALB/c mice during the sensitization period also abolished the induction of asthmatic responses. In contrast, administration of anti-OX40L mAb during the challenge period did not inhibit the asthmatic responses. These results indicate a critical role for OX40L in the induction phase, which leads to the development of pathogenic Th2 cells, but not in the effector phase, which includes migration and activation of pathogenic Th2 cells in the lung.
引用
收藏
页码:861 / 869
页数:9
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