Murdoch J R, Gregory L G, Lloyd C M
Leukocyte Biology Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
Clin Exp Allergy. 2014 Nov;44(11):1386-98. doi: 10.1111/cea.12395.
γδT cells play a crucial immunoregulatory role in the lung, maintaining normal airway tone and preventing hyperresponsiveness to innocuous allergen. During acute inflammatory episodes, γδT cells promote resolution of acute inflammation. However, their contribution to inflammation-associated airway remodelling remains unexplored. Here we investigate the effects of γδT cell blockade on established allergic airway inflammation and development of remodelling.
Sensitised mice were exposed to prolonged ovalbumin challenge or continuous house-dust mite exposure to induce chronic inflammation and remodelling. Functional blocking anti-TCRδ antibody was administered therapeutically, and parameters of airway inflammation and remodelling were examined.
Therapeutic blockade of γδT cells prevented the typical resolution of acute airway inflammation characterised by elevated eosinophil and Th2 cell numbers. Moreover, the lung displayed exacerbated airway remodelling, typified by excess peribronchiolar collagen deposition.
These results demonstrate a unique role for γδT cells in constraining allergen-induced airway remodelling. Manipulating the γδT cell compartment may therefore contribute to strategies to prevent and treat remodelling.
γδT细胞在肺部发挥关键的免疫调节作用，维持正常气道张力并防止对无害过敏原产生高反应性。在急性炎症发作期间，γδT细胞促进急性炎症的消退。然而，它们对炎症相关气道重塑的作用仍未得到探索。在此，我们研究γδT细胞阻断对已建立的过敏性气道炎症和重塑发展的影响。
致敏小鼠暴露于延长的卵清蛋白激发或持续的屋尘螨暴露，以诱导慢性炎症和重塑。给予功能性阻断抗TCRδ抗体进行治疗，并检查气道炎症和重塑的参数。
γδT细胞的治疗性阻断阻止了以嗜酸性粒细胞和Th2细胞数量增加为特征的急性气道炎症的典型消退。此外，肺表现出加剧的气道重塑，其典型特征是支气管周围胶原沉积过多。
这些结果证明γδT细胞在限制过敏原诱导的气道重塑中具有独特作用。因此，操纵γδT细胞区室可能有助于预防和治疗重塑的策略。
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