title: γδT cells suppress inflammation and disease during rhinovirus-induced asthma exacerbations.
abstract: Most asthma exacerbations are triggered by virus infections, the majority being caused by human rhinoviruses (RV). In mouse models, γδT cells have been previously demonstrated to influence allergen-driven airways hyper-reactivity (AHR) and can have antiviral activity, implicating them as prime candidates in the pathogenesis of asthma exacerbations. To explore this, we have used human and mouse models of experimental RV-induced asthma exacerbations to examine γδT-cell responses and determine their role in the immune response and associated airways disease. In humans, airway γδT-cell numbers were increased in asthmatic vs. healthy control subjects during experimental infection. Airway and blood γδT-cell numbers were associated with increased airways obstruction and AHR. Airway γδT-cell number was also positively correlated with bronchoalveolar lavage (BAL) virus load and BAL eosinophils and lymphocytes during RV infection. Consistent with our observations of RV-induced asthma exacerbations in humans, infection of mice with allergic airways inflammation increased lung γδT-cell number and activation. Inhibiting γδT-cell responses using anti-γδTCR (anti-γδT-cell receptor) antibody treatment in the mouse asthma exacerbation model increased AHR and airway T helper type 2 cell recruitment and eosinophilia, providing evidence that γδT cells are negative regulators of airways inflammation and disease in RV-induced asthma exacerbations.
authors: Airways Disease Infection Section, National Heart and Lung Institute, Imperial College London; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Centre for Respiratory Infections, London, UK.
authors: N
authors: N
authors: Glanville
authors: S D
authors: SD
authors: Message
authors: R P
authors: RP
authors: Walton
authors: R M
authors: RM
authors: Pearson
authors: H L
authors: HL
authors: Parker
authors: V
authors: V
authors: Laza-Stanca
authors: P
authors: P
authors: Mallia
authors: T
authors: T
authors: Kebadze
authors: M
authors: M
authors: Contoli
authors: O M
authors: OM
authors: Kon
authors: A
authors: A
authors: Papi
authors: L A
authors: LA
authors: Stanciu
authors: S L
authors: SL
authors: Johnston
authors: N W
authors: NW
authors: Bartlett
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001249:Asthma / Q000209:etiology / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010850:Picornaviridae Infections / Q000150:complications / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D012229:Rhinovirus; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta
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