Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms remain not fully understood. In this study, we have used wild type C57BL/6 and CD4 knockout (CD4KO) mouse models to better understand the roles of the CD4 T cells and cellular mechanisms responsible for enhanced respiratory disease after FI-RSV vaccination and RSV infection. Less eosinophil infiltration and lower pro-inflammatory cytokine production were observed in FI-RSV vaccinated CD4KO mice after RSV infection compared to FI-RSV vaccinated C57BL/6 mice. NK cells and cytokine-producing CD8 T cells were recruited at high levels in the airways of CD4KO mice, correlating with reduced respiratory disease. Depletion studies provided evidence that virus control was primarily mediated by NK cells whereas CD8 T cells contributed to IFN-γ production and less eosinophilic lung inflammation. This study demonstrated the differential roles of effector CD4 and CD8 T cells as well as NK cells, in networking with other inflammatory infiltrates in RSV disease in immune competent and CD4-deficient condition.

中文翻译：

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自然杀伤和 CD8 T 细胞有助于在 CD4 缺陷条件下通过福尔马林灭活呼吸道合胞病毒疫苗接种提供保护

呼吸道合胞病毒 (RSV) 会导致婴儿、幼儿和老年人的严重肺部疾病。由于疫苗增强呼吸道疾病，福尔马林灭活 RSV (FI-RSV) 疫苗试验失败，但潜在的免疫机制仍未完全了解。在这项研究中，我们使用野生型 C57BL/6 和 CD4 基因敲除 (CD4KO) 小鼠模型来更好地了解 CD4 T 细胞的作用以及导致 FI-RSV 疫苗接种和 RSV 感染后呼吸道疾病加重的细胞机制。与 FI-RSV 接种的 C57BL/6 小鼠相比，在 RSV 感染后，在 FI-RSV 接种的 CD4KO 小鼠中观察到较少的嗜酸性粒细胞浸润和较低的促炎细胞因子产生。NK 细胞和产生细胞因子的 CD8 T 细胞在 CD4KO 小鼠的气道中以高水平募集，这与呼吸道疾病的减少有关。耗竭研究提供的证据表明，病毒控制主要由 NK 细胞介导，而 CD8 T 细胞有助于 IFN-γ 的产生和较少的嗜酸性肺部炎症。这项研究证明了效应 CD4 和 CD8 T 细胞以及 NK 细胞在免疫功能正常和 CD4 缺陷的 RSV 疾病中与其他炎症浸润网络的不同作用。