γδT cells suppress inflammation and disease during rhinovirus-induced asthma exacerbations.
γδT cells suppress inflammation and disease during rhinovirus-induced asthma exacerbations.
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大多数哮喘急性发作是由病毒感染引起的，其中大多数是由人鼻病毒（RV）引起的。在小鼠模型中，γδT细胞先前已被证明可影响变应原驱动的气道高反应性（AHR），并可具有抗病毒活性，表明它们是哮喘急性发作发病机制的主要候选者。为了探索这一点，我们使用了实验性RV诱导的哮喘急性发作的人类和小鼠模型来检查γδ T细胞应答，并确定它们在免疫应答和相关气道疾病中的作用。在人类中，在实验感染期间，哮喘受试者与健康对照受试者相比气道γδ T细胞数量增加。气道和血液γδ T细胞数量与气道阻塞和AHR增加相关。在RV感染期间，气道γδ T细胞数量也与支气管肺泡灌洗（BAL）病毒载量、BAL嗜酸性粒细胞和淋巴细胞呈正相关。与我们对RV诱导的人类哮喘加重的观察结果一致，小鼠过敏性气道炎症感染增加了肺γδ T细胞数量和活化。在小鼠哮喘急性发作模型中，使用抗γδTCR（抗γδ T细胞受体）抗体治疗抑制γδ T细胞应答增加了AHR和气道辅助性T细胞2型募集和嗜酸性粒细胞增多，这提供了γδT细胞是RV诱导的哮喘急性发作中气道炎症和疾病的负调节因子的证据。
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.
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