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This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/L307    most recent 00521.2007v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Burchell, J. T. Articles by Turner, D. J. Search for Related Content PubMed PubMed Citation Articles by Burchell, J. T. Articles by Turner, D. J.

Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells

Divisions of ¹Clinical Sciences and ²Cell Biology, Telethon Institute for Child Health Research, Subiaco; ³Centre for Child Health Research, University of Western Australia, Nedlands; and ⁴Division of Health Sciences, Murdoch University, Murdoch, Western Australia

Submitted 16 December 2007 ; accepted in final form 12 November 2008

Understanding the mechanisms involved in respiratory tolerance to inhaled allergens could potentially result in improved therapies for asthma and allergic diseases. Airway hyperresponsiveness (AHR) is a major feature of allergic asthma, thus the aim of the current study was to investigate mechanisms underlying suppression of allergen-induced AHR during chronic allergen exposure. Adult BALB/c mice were systemically sensitized with ovalbumin (OVA) in adjuvant and then challenged with a single 3 or 6 wk of OVA aerosols. Airway and parenchymal responses to inhaled methacholine (MCh), inflammatory cell counts, cytokines, OVA-specific IgE and IgG₁, parenchymal histology, and numbers of airway CD4⁺69⁺ activated and CD4⁺25⁺FoxP3⁺ regulatory T (Treg) cells were assessed 24 h after the final aerosol. Single OVA challenge resulted in AHR, eosinophilia, increased serum OVA-specific IgE, and T helper 2 (Th2) cytokines in bronchoalveolar lavage (BAL) but no difference in numbers of Treg compared with control mice. Three weeks of OVA challenges resulted in suppression of AHR and greater numbers of airway Treg cells and increased transforming growth factor-β₁ (TGFβ₁) compared with control mice despite the presence of increased eosinophilia, OVA-specific IgE and IgG₁, and airway remodeling. Six weeks of OVA challenges restored AHR, whereas airway Treg numbers, TGFβ₁, BAL eosinophilia, and Th2 cytokines returned to control levels. Partial in vivo depletion or adoptive transfer of Treg cells restored or inhibited AHR, respectively, but did not affect TGFβ₁ or Th2 cytokine production. In conclusion, AHR suppression is mediated by airway Treg cells and potentially via a paracrine induction of TGFβ₁ in the airways.

asthma; T regulatory cell; lung function