期刊
LABORATORY INVESTIGATION
卷 82, 期 4, 页码 455-462出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1038/labinvest.3780438
关键词
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Asthma is an acute-on-chronic inflammatory disease of the airways, characterized by airflow obstruction and hyper-reactivity of the airways to a variety of stimuli. Chronic asthma is associated with remodeling of the airway wall, which may contribute to hyper-reactivity and fixed airflow obstruction. We used an improved mouse model of chronic asthma to investigate the role of CD4(+) T-lymphocytes in airway remodeling and hyper-reactivity. Animals functionally depleted of CD4(+) T-lymphocytes by repeated administration of a monoclonal antibody exhibited markedly decreased airway responsiveness. In addition, these mice had greatly diminished subepithelial fibrosis, epithelial thickening, and mucous cell hyperplasia/metaplasia. Chronic inflammation in the airway wall was moderately reduced, with a marked decrease in the accumulation of immunoglobulin-synthesizing plasma cells. However, intraepithelial accumulation of eosinophils was not significantly inhibited and airway epithelial expression of eotaxin was undiminished. This work provides the first experimental evidence that CD4(+) T-lymphocytes play a crucial role in the pathogenesis of the lesions of chronic asthma and ends support to the notion that functional inhibition of these cells may be an important therapeutic target.
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