Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells

Strickland, Deborah H., Stumbles, Philip A., Zosky, Graeme R., Subrata, Lily S., Thomas, Jenny A., Turner, Debra J., Sly, Peter D. and Holt, Patrick G. (2006) Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. Journal of Experimental Medicine, 203 12: 2649-2660. doi:10.1084/jem.20060155

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Author Strickland, Deborah H.
Stumbles, Philip A.
Zosky, Graeme R.
Subrata, Lily S.
Thomas, Jenny A.
Turner, Debra J.
Sly, Peter D.
Holt, Patrick G.
Title Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells
Formatted title
Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
1540-9538
Publication date 2006-11-27
Sub-type Article (original research)
DOI 10.1084/jem.20060155
Open Access Status File (Publisher version)
Volume 203
Issue 12
Start page 2649
End page 2660
Total pages 12
Place of publication New York, United States
Publisher Rockefeller University Press
Language eng
Formatted abstract
An important feature of atopic asthma is the T cell–driven late phase reaction involving transient bronchoconstriction followed by development of airways hyperresponsiveness (AHR). Using a unique rat asthma model we recently showed that the onset and duration of the aeroallergen-induced airway mucosal T cell activation response in sensitized rats is determined by the kinetics of functional maturation of resident airway mucosal dendritic cells (AMDCs) mediated by cognate interactions with CD4+ T helper memory cells. The study below extends these investigations to chronic aeroallergen exposure. We demonstrate that prevention of ensuing cycles of T cell activation and resultant AHR during chronic exposure of sensitized rats to allergen aerosols is mediated by CD4+CD25+Foxp3+LAG3+ CTLA+CD45RC+ T cells which appear in the airway mucosa and regional lymph nodes within 24 h of initiation of exposure, and inhibit subsequent Th-mediated upregulation of AMDC functions. These cells exhibit potent regulatory T (T reg) cell activity in both in vivo and ex vivo assay systems. The maintenance of protective T reg activity is absolutely dependent on continuing allergen stimulation, as interruption of exposure leads to waning of T reg activity and reemergence of sensitivity to aeroallergen exposure manifesting as AMDC/T cell upregulation and resurgence of T helper 2 cytokine expression, airways eosinophilia, and AHR.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 17 Nov 2010, 11:52:46 EST