Department of Microbiology and Immunology, University of Rochester, New York.
Department of Medicine, University of Rochester, New York.
J Infect Dis. 2018 Jul 2;218(3):418-428. doi: 10.1093/infdis/jiy016.
The pathogenesis of respiratory syncytial virus (RSV) in older adults may be due to age-related T-cell immunosenescence. Thus, we evaluated CD4 and CD8 T-cell responses during RSV infection in adults across the age spectrum.
Peripheral blood mononuclear cells collected during RSV infection in adults, age 26-96 years, were stimulated with live RSV and peptide pools representing F, M, NP, and G proteins and analyzed by flow cytometry.
There were no significant age-related differences in frequency of CD4+ T cells synthesizing interferon (IFN)γ, interleukin (IL)2, IL4, IL10, or tumor necrosis factor (TNF)α or in CD8+IFNγ+ T cells. IL4+CD4+ T-cell numbers were low, as were IL13 and IL17 responses. However, in univariate analysis, CD4 T-cell IFNγ, IL2, IL4, IL10, and TNFα responses and CD8+IFNγ+ T cells were significantly increased with more severe illness requiring hospitalization. In multivariate analysis, viral load was also associated with increased T-cell responses.
We found no evidence of diminished RSV-specific CD4 or CD8 T-cell responses in adults infected with RSV. However, adults with severe disease seemed to have more robust CD4 and CD8 T-cell responses during infection, suggesting that disease severity may have a greater association with T-cell responses than age.
呼吸道合胞病毒(RSV)在老年人中的发病机制可能与年龄相关的 T 细胞免疫衰老有关。因此,我们评估了不同年龄段成年人在 RSV 感染期间 CD4 和 CD8 T 细胞的反应。
收集 26-96 岁成年人在 RSV 感染期间的外周血单核细胞,用活 RSV 和代表 F、M、NP 和 G 蛋白的肽库刺激,并通过流式细胞术进行分析。
CD4+T 细胞合成干扰素(IFN)γ、白细胞介素(IL)2、IL4、IL10 或肿瘤坏死因子(TNF)α的频率或 CD8+IFNγ+T 细胞中没有与年龄相关的显著差异。IL4+CD4+T 细胞数量较少,IL13 和 IL17 反应也较少。然而,在单因素分析中,CD4 T 细胞 IFNγ、IL2、IL4、IL10 和 TNFα反应和 CD8+IFNγ+T 细胞随着需要住院治疗的更严重疾病而显著增加。在多变量分析中,病毒载量也与增加的 T 细胞反应相关。
我们没有发现 RSV 感染的成年人中 RSV 特异性 CD4 或 CD8 T 细胞反应减弱的证据。然而,患有严重疾病的成年人在感染期间似乎有更强的 CD4 和 CD8 T 细胞反应,这表明疾病严重程度与 T 细胞反应的关联可能大于年龄。