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: Takeshi Nabe, Toyoko Morishita, Kouki Matsuya, Ayumu Ikedo, Masanori Fujii, Nobuaki Mizutani, Shin Yoshino
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 116 Issue 4 Pg. 373-83 ( 2011) ISSN: 1347-8648 [Electronic] Japan
• PMID: 21778663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Interleukin-5
• Dexamethasone
• Ovalbumin

Topics

• Airway Remodeling (immunology)
• Airway Resistance (immunology)
• Animals
• Antibodies, Monoclonal (immunology)
• Asthma (immunology, pathology)
• Bronchi (pathology)
• Bronchial Hyperreactivity (immunology, pathology)
• CD4-Positive T-Lymphocytes (immunology, pathology)
• Dexamethasone (pharmacology)
• Eosinophilia (immunology, pathology)
• Epithelial Cells (immunology, pathology)
• Fibrosis (immunology, pathology)
• Inflammation (immunology, pathology)
• Interleukin-5 (biosynthesis, immunology)
• Mice
• Mice, Inbred BALB C
• Muscle, Smooth (immunology, pathology)
• Ovalbumin (immunology)
• Th2 Cells (immunology, pathology)