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

D.H. Strickland; P.A. Stumbles; G.R. Zosky; L.S. Subrata; J.A. Thomas; D.J. Turner; P.D. Sly; P.G. Holt

doi:10.1084/jem.20060155

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

Journal article

Open access

Peer reviewed

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

D.H. Strickland, P.A. Stumbles, G.R. Zosky, L.S. Subrata, J.A. Thomas, D.J. Turner, P.D. Sly and P.G. Holt

Journal of Experimental Medicine, Vol.203(12), pp.2649-2660

2006

DOI: https://doi.org/10.1084/jem.20060155

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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.

Details

Title: Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells
Authors/Creators: D.H. Strickland (Author/Creator)
P.A. Stumbles (Author/Creator)
G.R. Zosky (Author/Creator)
L.S. Subrata (Author/Creator)
J.A. Thomas (Author/Creator)
D.J. Turner (Author/Creator)
P.D. Sly (Author/Creator)
P.G. Holt (Author/Creator)
Publication Details: Journal of Experimental Medicine, Vol.203(12), pp.2649-2660
Publisher: The Rockefeller University Press
Identifiers: 991005543773507891
Copyright: 2006 Rockefeller University Press
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.487 Regulatory T Cells
Web Of Science research areas: Immunology; Medicine, Research & Experimental
ESI research areas: Immunology