Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Sci Rep. 2022 Jan 7;12(1):135. doi: 10.1038/s41598-021-03936-y.
Interleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following influenza infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of influenza-specific CD8 T cells therein. We show that IL-7 plays a cell-intrinsic role in the accumulation of NP and PA-specific CD8 T cells in the lymph node. We also found that IL-7 shapes terminal differentiation, degranulation and cytokine production to a greater extent in PA-specific than NP-specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.
白细胞介素-7（IL-7）是一种细胞因子，其在 T 细胞发育和存活中的重要性已得到广泛认可。然而，IL-7 如何在急性病毒感染期间影响 CD8 T 细胞反应还不太清楚。我们之前的研究表明，IL-7 信号缺陷小鼠在流感感染后流感特异性 CD8 T 细胞的积累减少。我们试图确定 IL-7 是否会影响急性病毒感染期间 CD8 T 细胞在纵隔淋巴结中的早期扩增和在肺部的效应功能。通过使用 IL-7Rα 信号缺陷小鼠，我们发现 IL-7 对于纵隔淋巴结的正常大小和其中流感特异性 CD8 T 细胞的早期克隆扩增是必需的。我们还发现，IL-7 在淋巴结中对 NP 和 PA 特异性 CD8 T 细胞的积累起着细胞内在的作用。我们还发现，IL-7 在 PA 特异性 CD8 T 细胞中的终末分化、脱颗粒和细胞因子产生方面的影响大于 NP 特异性 CD8 T 细胞。此外，我们证明病毒感染会诱导肺部组织中产生 IL-7，并且我们还描述了多种细胞来源，这些细胞来源对 IL-7 的产生有贡献。我们关于 IL-7 及其对下呼吸道疾病影响的研究结果对于扩大当前可用治疗方法的应用范围将非常重要。
