Jarjour Nicholas N, Dalzell Talia S, Maurice Nicholas J, Wanhainen Kelsey M, Peng Changwei, DePauw Taylor A, Block Katharine E, Valente William J, Ashby K Maude, Masopust David, Jameson Stephen C
Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
bioRxiv. 2024 Jun 3:2024.05.31.596695. doi: 10.1101/2024.05.31.596695.
Interleukin-7 (IL-7) is considered a critical regulator of memory CD8 T cell homeostasis, but this is primarily based on analysis of circulating and not tissue-resident memory (T) subsets. Furthermore, the cell-intrinsic requirement for IL-7 signaling during memory homeostasis has not been directly tested. Using inducible deletion, we found that loss had only a modest effect on persistence of circulating memory and T subsets and that IL-7Rα was primarily required for normal basal proliferation. Loss of IL-15 signaling imposed heightened IL-7Rα dependence on memory CD8 T cells, including T populations previously described as IL-15-independent. In the absence of IL-15 signaling, IL-7Rα was upregulated, and loss of IL-7Rα signaling reduced proliferation in response to IL-15, suggesting cross-regulation in memory CD8 T cells. Thus, across subsets and tissues, IL-7 and IL-15 act in concert to support memory CD8 T cells, conferring resilience to altered availability of either cytokine.
白细胞介素-7（IL-7）被认为是记忆性CD8 T细胞稳态的关键调节因子，但这主要基于对循环而非组织驻留记忆T细胞亚群的分析。此外，记忆稳态期间IL-7信号传导的细胞内在需求尚未得到直接测试。通过诱导性缺失，我们发现缺失对循环记忆和T细胞亚群的持久性仅有适度影响，并且IL-7Rα主要是正常基础增殖所必需的。IL-15信号的缺失增强了记忆性CD8 T细胞对IL-7Rα的依赖性，包括先前被描述为不依赖IL-15的T细胞群体。在没有IL-15信号的情况下，IL-7Rα上调，并且IL-7Rα信号的缺失降低了对IL-15的反应性增殖，提示记忆性CD8 T细胞存在交叉调节。因此，在各个亚群和组织中，IL-7和IL-15协同作用以支持记忆性CD8 T细胞，赋予对任一细胞因子可用性改变的恢复力。
