title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Cristan
authors.initials: C
authors.lastname: Herbert
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Kumar
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D007091:Image Processing, Computer-Assisted; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013047:Specific Pathogen-Free Organisms
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D016210:Methacholine Chloride; D010047:Ovalbumin