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

journal contribution
posted on 2023-05-17, 22:54 authored by Strickland, DH, Stumbles, PA, Graeme ZoskyGraeme Zosky, Subrata, LS, Thomas, JA, Turner, DJ, Sly, PD, Holt, PG
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.

History

Publication title

The Journal of Experimental Medicine

Volume

203

Issue

12

Pagination

2649-60

ISSN

0022-1007

Department/School

Tasmanian School of Medicine

Publisher

Rockefeller Univ Press

Place of publication

1114 First Ave, 4Th Fl, New York, USA, Ny, 10021

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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