Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells
Strickland, D.H., Stumbles, P.A., Zosky, G.R., Subrata, L.S., Thomas, J.A., Turner, D.J., Sly, P.D. and Holt, P.G. (2006) Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. Journal of Experimental Medicine, 203 (12). pp. 2649-2660.
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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.
|Publication Type:||Journal Article|
|Publisher:||The Rockefeller University Press|
|Copyright:||2006 Rockefeller University Press|
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