Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.
Nat Commun. 2020 Jun 5;11(1):2857. doi: 10.1038/s41467-020-16633-7.
Virtual memory T (T) cells are antigen-naïve CD8 T cells that exist in a semi-differentiated state and exhibit marked proliferative dysfunction in advanced age. High spare respiratory capacity (SRC) has been proposed as a defining metabolic characteristic of antigen-experienced memory T (T) cells, facilitating rapid functionality and survival. Given the semi-differentiated state of T cells and their altered functionality with age, here we investigate T cell metabolism and its association with longevity and functionality. Elevated SRC is a feature of T, but not T, cells and it increases with age in both subsets. The elevated SRC observed in aged mouse T cells and human CD8 T cells from older individuals is associated with a heightened sensitivity to IL-15. We conclude that elevated SRC is a feature of T, but not T, cells, is driven by physiological levels of IL-15, and is not indicative of enhanced functionality in CD8 T cells.
初始 T（T）细胞是处于半分化状态的抗原-naive CD8 T 细胞，在老年时表现出明显的增殖功能障碍。高备用呼吸能力（SRC）被提出作为抗原经验记忆 T（T）细胞的定义代谢特征，促进快速功能和存活。鉴于 T 细胞的半分化状态及其随年龄变化的功能改变，我们在此研究 T 细胞代谢及其与长寿和功能的关系。高 SRC 是 T 细胞的特征，而不是 T 细胞的特征，在两个亚群中都会随年龄增长而增加。在老年小鼠 T 细胞和来自老年人的人 CD8 T 细胞中观察到的升高的 SRC 与对 IL-15 的敏感性增加有关。我们得出结论，高 SRC 是 T 细胞的特征，而不是 T 细胞的特征，由生理水平的 IL-15 驱动，并且不能表明 CD8 T 细胞的功能增强。
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