title: Complete dependence on CD4+ cells in late asthmatic response, but limited contribution of the cells to airway remodeling in sensitized mice.
abstract: It is known that the late asthmatic response (LAR), a characteristic feature of asthma, is closely associated with CD4+ Th2 cell-mediated allergic inflammation. Airway remodeling is also a pathogenesis of asthma, but literature reporting roles of CD4+ cells in the remodeling is controversial. There has been no study that simultaneously assessed the roles of CD4+ cells in both LAR and airway remodeling. Sensitized mice were intratracheally challenged with ovalbumin 4 times. Treatment with an anti-CD4 monoclonal antibody (mAb) before the 1st challenge almost completely abolished increase in CD4+ cells in the tissues after the 4th challenge. The late phase increase in airway resistance after the 4th challenge was also completely inhibited by anti-CD4 mAb. Parameters of airway remodeling, subepithelial fibrosis and epithelial thickening were attenuated by treatment, whereas the inhibition was only 30% - 40%. Bronchial smooth muscle thickening was not affected. Because interleukin (IL)-5 production as well as eosinophilia was effectively suppressed by anti-CD4 mAb, the effect of anti-IL-5 mAb was also examined, resulting in no inhibition of airway remodeling. Collectively, although the LAR was completely dependent on CD4+ cell activation, airway remodeling was only partially dependent on the cell.
authors.affiliation: Department of Pharmacology, Kyoto Pharmaceutical University, Japan. nabe@mb.kyoto-phu.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nabe
authors.forename: Toyoko
authors.initials: T
authors.lastname: Morishita
authors.forename: Kouki
authors.initials: K
authors.lastname: Matsuya
authors.forename: Ayumu
authors.initials: A
authors.lastname: Ikedo
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Mizutani
authors.forename: Shin
authors.initials: S
authors.lastname: Yoshino
mesh_terms: D056151:Airway Remodeling / Q000276:immunology*; D000403:Airway Resistance / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005355:Fibrosis / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D003907:Dexamethasone; D010047:Ovalbumin