The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the specific features of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a state-of-the-art model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4 and CD8 T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.

中文翻译：

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新生儿肺部发育中的T细胞区室的特定特征是呼吸道合胞病毒免疫发病机制的决定因素

人呼吸道合胞病毒（RSV）是婴儿严重下呼吸道感染的主要原因，可能是由于未成熟的新生儿肺部免疫系统的特定特征所致。我们使用新生羔羊，人类肺部发育的经典模型和RSV感染的最新模型，旨在探讨生命早期细胞介导的免疫在RSV疾病中的作用。值得注意的是，在健康状况下，新生肺的发育中的T细胞区室与成熟成年肺中的T细胞区室显示出主要差异。最引人注目的观察结果是，支气管肺泡产生IL-4的CD4和CD8 T细胞的基线频率很高，随着发育年龄的增长，基线频率逐渐下降。RSV感染加剧了支气管肺泡空间中的pro 2型环境，而不是引起2型反应本身。此外，调节性T细胞的抑制功能很早就出现，以减弱2型亲环境，而不是随后将其关闭，而γδT细胞下降而不能产生IL-17。重要的是，RSV疾病的严重程度与那些非常规支气管肺泡T细胞反应的程度有关。这些发现为人们早期发现RSV免疫发病机理提供了新颖的见解，并为理解RSV疾病的严重性迈出了重要的一步。RSV疾病的严重程度与那些非常规支气管肺泡T细胞反应的程度有关。这些发现为人们早期发现RSV免疫发病机理提供了新颖的见解，并为理解RSV疾病的严重性迈出了重要的一步。RSV疾病的严重程度与那些非常规支气管肺泡T细胞反应的程度有关。这些发现为人们早期发现RSV免疫发病机理提供了新颖的见解，并为了解RSV疾病的严重性迈出了重要的一步。