Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
The Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
Sci Immunol. 2020 Nov 6;5(53). doi: 10.1126/sciimmunol.abc4557.
Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8 tissue-resident memory T cells (T) in the respiratory tract of aged hosts. T cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that T cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, T cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8 T cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated T cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.
下呼吸道病毒感染,如流感病毒和严重急性呼吸综合征冠状病毒 2 感染,常导致老年个体发生严重病毒性肺炎。在这里,我们报告流感病毒性肺炎导致慢性未解决的肺部病理学,并加剧了呼吸道中 CD8 组织驻留记忆 T 细胞(T 细胞)在老年宿主中的积累。T 细胞的积累依赖于老化组织中存在的升高的 TGF-β。此外,我们表明,从老年肺部分离的 T 细胞缺乏一个特征在于参与 TCR 信号和效应功能的分子表达的亚群。因此,来自老年肺部的 T 细胞不足以提供异源保护性免疫。耗尽 CD8 T 细胞可抑制持续性慢性肺部炎症,并改善老年但非年轻动物的组织纤维化。总的来说,我们的数据表明,与年龄相关的 T 细胞功能障碍支持病毒性肺炎后慢性肺部炎症和纤维化后遗症。