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- Title
Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells.
- Authors
Strickland, Deborah H; Stumbles, Philip A; Zosky, Graeme R; Subrata, Lily S; Thomas, Jenny A; Turner, Debra J; Sly, Peter D; Holt, Patrick G
- 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.
- Publication
The Journal of experimental medicine, 2006, Vol 203, Issue 12, p2649
- ISSN
0022-1007
- Publication type
Journal Article
- DOI
10.1084/jem.20060155