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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/L373    most recent 00053.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zosky, G. R. Articles by Stumbles, P. A. PubMed PubMed Citation Articles by Zosky, G. R. Articles by Stumbles, P. A.

Airway hyperresponsiveness is associated with activated CD4⁺ T cells in the airways

Divisions of ¹Clinical Sciences and ²Cell Biology, Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia; and ³School of Veterinary and Biomedical Science, Faculty of Health Sciences, Murdoch University, Perth, Australia

Submitted 19 February 2009 ; accepted in final form 25 May 2009

It is widely accepted that atopic asthma depends on an allergic response in the airway, yet the immune mechanisms that underlie the development of airway hyperresponsiveness (AHR) are poorly understood. Mouse models of asthma have been developed to study the pathobiology of this disease, but there is considerable strain variation in the induction of allergic disease and AHR. The aim of this study was to compare the development of AHR in BALB/c, 129/Sv, and C57BL/6 mice after sensitization and challenge with ovalbumin (OVA). AHR to methacholine was measured using a modification of the forced oscillation technique in anesthetized, tracheostomized mice to distinguish between airway and parenchymal responses. Whereas all strains showed signs of allergic sensitization, BALB/c was the only strain to develop AHR, which was associated with the highest number of activated (CD69⁺) CD4⁺ T cells in the airway wall and the highest levels of circulating OVA-specific IgG₁. AHR did not correlate with total or antigen-specific IgE. We assessed the relative contribution of CD4⁺ T cells and specific IgG₁ to the development of AHR in BALB/c mice using adoptive transfer of OVA-specific CD4⁺ T cells from DO11.10 mice. AHR developed in these mice in a progressive fashion following multiple OVA challenges. There was no evidence that antigen-specific antibody had a synergistic effect in this model, and we concluded that the number of antigen-specific T cells activated and recruited to the airway wall was crucial for development of AHR.

mouse models of asthma; forced oscillation technique; BALB/c; 129/Sv; C57BL/6