REQUIREMENTS FOR ALLERGEN-INDUCED AIRWAY HYPERREACTIVITY IN T-CELL-DEFICIENT AND B-CELL-DEFICIENT MICE

Citation
Db. Corry et al., REQUIREMENTS FOR ALLERGEN-INDUCED AIRWAY HYPERREACTIVITY IN T-CELL-DEFICIENT AND B-CELL-DEFICIENT MICE, Molecular medicine, 4(5), 1998, pp. 344-355
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Cell Biology
Journal title
ISSN journal
1076-1551
Volume
4
Issue
5
Year of publication
1998
Pages
344 - 355
Database
ISI
SICI code
1076-1551(1998)4:5<344:RFAAHI>2.0.ZU;2-E
Abstract
Background: The pathogenesis of asthma is believed to reflect antigen- induced airway inflammation leading to the recruitment of eosinophils and activation of mast cells through cell-associated IgE. Controversie s persist however, regarding the relative importance of different path ogenic cells and effector molecules. Materials and Methods: A variety of gene-targeted mice were examined for the induction of cholinergic a irway hyperresponsiveness (AH), allergic airway inflammation, mucus pr oduction, and serum IgE reactivity following intratracheal challenge w ith a potent allergen. AH was determined using whole-body plethysmogra phy following acetylcholine challenge. Where possible, results were co nfirmed using neutralizing antibodies and cell-specific reconstitution of immune deficient mice. Results: T and B cell-deficient, recombinas e-activating-gene-deficient mice (RAG -/-) failed to develop significa nt allergic inflammation and AH following allergen challenge. Reconsti tution of RAG -/- mice with CD4(+) T cells alone was sufficient to res tore allergen-induced AH, allergic inflammation and goblet cell hyperp lasia, but not IgE reactivity. Sensitized B cell-deficient mice also d eveloped airway hyperreactivity and lung inflammation comparable to th at of wild-type animals, confirming that antibodies were dispensable. Treatment with neutralizing anti-IL-4 antibody or sensitization of IL- 4-deficient mice resulted in loss of airway hyperreactivity, whereas t reatment with anti-IL-5 antibody or sensitization of IL-5-deficient mi ce had no effect. Conclusions: In mice, CD4(+) T cells are alone suffi cient to mediate many of the pathognomonic changes that occur in human asthma by a mechanism dependent upon IL-4, but independent of IL-5, I gE, or both. Clarification of the role played by CD4(+) T cells is lik ely to stimulate important therapeutic advances in treatment of asthma .