Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Nat Med. 2012 Oct;18(10):1525-30. doi: 10.1038/nm.2896. Epub 2012 Sep 9.
Immune tolerance is instituted early in life, during which time regulatory T (T(reg)) cells have an important role. Recurrent infections with respiratory syncytial virus (RSV) in early life increase the risk for asthma in adult life. Repeated infection of infant mice tolerized to ovalbumin (OVA) through their mother's milk with RSV induced allergic airway disease in response to OVA sensitization and challenge, including airway inflammation, hyper-reactivity and higher OVA-specific IgE, as compared to uninfected tolerized control mice. Virus infection induced GATA-3 expression and T helper type 2 (T(H)2) cytokine production in forkhead box P3 (FOXP3)(+) T(reg) cells and compromised the suppressive function of pulmonary T(reg) cells in a manner that was dependent on interleukin-4 receptor α (IL-4Rα) expression in the host. Thus, by promoting a T(H)2-type inflammatory response in the lung, RSV induced a T(H)2-like effector phenotype in T(reg) cells and attenuated tolerance to an unrelated antigen (allergen). Our findings highlight a mechanism by which viral infection targets a host-protective mechanism in early life and increases susceptibility to allergic disease.
免疫耐受是在生命早期建立的，在此期间调节性 T（Treg）细胞起着重要作用。生命早期反复感染呼吸道合胞病毒（RSV）会增加成年期哮喘的风险。通过母亲的乳汁使婴儿期耐受卵清蛋白（OVA）的小鼠反复感染 RSV 会导致对 OVA 致敏和激发的过敏性气道疾病，包括气道炎症、高反应性和更高的 OVA 特异性 IgE，与未感染的耐受对照小鼠相比。病毒感染诱导叉头框 P3（FOXP3）（+）T 调节（Treg）细胞中的 GATA-3 表达和辅助性 T 细胞 2（T(H)2）细胞因子产生，并以依赖于宿主中白细胞介素-4 受体α（IL-4Rα）表达的方式损害肺 Treg 细胞的抑制功能。因此，RSV 通过在肺部促进 T(H)2 型炎症反应，诱导 Treg 细胞产生类似于 T(H)2 的效应表型，并减弱对无关抗原（变应原）的耐受性。我们的研究结果强调了一种机制，即病毒感染针对生命早期的宿主保护性机制，并增加了对过敏性疾病的易感性。
