HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 97/6/2258    most recent 00597.2004v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Leigh, R. Articles by Inman, M. D. Search for Related Content PubMed PubMed Citation Articles by Leigh, R. Articles by Inman, M. D.

T-cell-mediated inflammation does not contribute to the maintenance of airway dysfunction in mice

¹Firestone Institute for Respiratory Health, Department of Medicine, and ²Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 4A6

Submitted 16 June 2004 ; accepted in final form 27 July 2004

T-cell-mediated airway inflammation is considered to be critical in the pathogenesis of airway hyperresponsiveness (AHR). We have described a mouse model in which chronic allergen exposure results in sustained AHR and aspects of airway remodeling and here sought to determine whether eliminating CD4⁺ and CD8⁺ cells, at a time when airway remodeling had occurred, would attenuate this sustained AHR. Sensitized BALB/c mice were subjected to either brief or chronic periods of allergen exposure and studied 24 h after brief or 4 wk after chronic allergen exposure. In both models, mice received three treatments with anti-CD4 and -CD8 monoclonal antibodies during the 10 days before outcome measurements. Outcomes included in vivo airway responsiveness to intravenous methacholine, CD4⁺ and CD8⁺ cell counts of lung and spleen using flow cytometric analysis, and airway morphometry using a computer-based image analysis system. Compared with saline control mice, brief allergen challenge resulted in AHR, which was eliminated by antibody treatment. Chronic allergen challenge resulted in sustained AHR and indexes of airway remodeling. This sustained AHR was not reversed by antibody treatment, even though CD4⁺ and CD8⁺ cells were absent in lung and spleen. These results indicate that T-cell-mediated inflammation is critical for development of AHR associated with brief allergen exposure, but is not necessary to maintain sustained AHR.

allergy; lung; T lymphocytes; rodent; bronchial hyperreactivity

This article has been cited by other articles:

				F. A. DiGiovanni, R. Ellis, J. Wattie, J. A. Hirota, D. S. Southam, and M. D. Inman Concurrent dual allergen exposure and its effects on airway hyperresponsiveness, inflammation and remodeling in mice Dis. Model. Mech., May 1, 2009; 2(5-6): 275 - 282. [Abstract] [Full Text] [PDF]

				T. A. Doherty, P. Soroosh, D. H. Broide, and M. Croft CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling Am J Physiol Lung Cell Mol Physiol, February 1, 2009; 296(2): L229 - L235. [Abstract] [Full Text] [PDF]

				D. S. Southam, R. Ellis, J. Wattie, W. Glass, and M. D. Inman Goblet Cell Rebound and Airway Dysfunction with Corticosteroid Withdrawal in a Mouse Model of Asthma Am. J. Respir. Crit. Care Med., December 1, 2008; 178(11): 1115 - 1122. [Abstract] [Full Text] [PDF]

				A. T. Nials and S. Uddin Mouse models of allergic asthma: acute and chronic allergen challenge Dis. Model. Mech., November 1, 2008; 1(4-5): 213 - 220. [Abstract] [Full Text] [PDF]

				D. S. Southam, R. Ellis, J. Wattie, S. Young, and M. D. Inman Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice Eur. Respir. J., October 1, 2008; 32(4): 970 - 978. [Abstract] [Full Text] [PDF]

				E. H. Walters, D. W. Reid, D. P. Johns, and C. Ward Nonpharmacological and pharmacological interventions to prevent or reduce airway remodelling Eur. Respir. J., September 1, 2007; 30(3): 574 - 588. [Abstract] [Full Text] [PDF]

				P. Forsythe, M. D. Inman, and J. Bienenstock Oral Treatment with Live Lactobacillus reuteri Inhibits the Allergic Airway Response in Mice Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 561 - 569. [Abstract] [Full Text] [PDF]

				C. Hubeau, I. Apostolou, and L. Kobzik Targeting of CD25 and Glucocorticoid-Induced TNF Receptor Family-Related Gene-Expressing T Cells Differentially Modulates Asthma Risk in Offspring of Asthmatic and Normal Mother Mice J. Immunol., February 1, 2007; 178(3): 1477 - 1487. [Abstract] [Full Text] [PDF]

				M. Witzenrath, B. Ahrens, S. M. Kube, A. Braun, H. G. Hoymann, A. C. Hocke, S. Rosseau, N. Suttorp, E. Hamelmann, and H. Schutte Detection of allergen-induced airway hyperresponsiveness in isolated mouse lungs Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L466 - L472. [Abstract] [Full Text] [PDF]

				M. M. Kelly, R. Leigh, P. Bonniaud, R. Ellis, J. Wattie, M. J. Smith, G. Martin, M. Panju, M. D. Inman, and J. Gauldie Epithelial Expression of Profibrotic Mediators in a Model of Allergen-Induced Airway Remodeling Am. J. Respir. Cell Mol. Biol., February 1, 2005; 32(2): 99 - 107. [Abstract] [Full Text] [PDF]