γδT cells suppress inflammation and disease during rhinovirus-induced asthma exacerbations

Most asthma exacerbations are triggered by virus infections, the majority being caused by human rhinoviruses (RV). In mouse models, gamma delta T 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 gamma delta T-cell responses and determine their role in the immune response and associated airways disease. In humans, airway gamma delta T-cell numbers were increased in asthmatic vs. healthy control subjects during experimental infection. Airway and blood gamma delta T-cell numbers were associated with increased airways obstruction and AHR. Airway gamma delta T-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 gamma delta T-cell number and activation. Inhibiting gamma delta T-cell responses using anti-gamma delta TCR (anti-gamma delta T-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 gamma delta T cells are negative regulators of airways inflammation and disease in RV-induced asthma exacerbations.