CD4(+) T-Lymphocytes Regulate Airway Remodeling and Hyper-Reactivity in a Mouse Model of Chronic Asthma

Abstract

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 lends support to the notion that functional inhibition of these cells may be an important therapeutic target. Show more