Cytotoxic CD8⁺ T cells play a key role in the elimination of intracellular infections and malignant cells and can provide long-term protective immunity. In the response to infection, CD8⁺ T cell metabolism is coupled to transcriptional, translational and epigenetic changes that are driven by extracellular metabolites and immunological signals. These programmes facilitate the adaptation of CD8⁺ T cells to the diverse and dynamic metabolic environments encountered in the circulation and in the tissues. In the setting of disease, both cell-intrinsic and cell-extrinsic metabolic cues contribute to CD8⁺ T cell dysfunction. In addition, changes in whole-body metabolism, whether through voluntary or disease-induced dietary alterations, can influence CD8⁺ T cell-mediated immunity. Defining the metabolic adaptations of CD8⁺ T cells in specific tissue environments informs our understanding of how these cells protect against pathogens and tumours and maintain tissue health at barrier sites. Here, we highlight recent findings revealing how metabolic networks enforce specific CD8⁺ T cell programmes and discuss how metabolism is integrated with CD8⁺ T cell differentiation and function and determined by environmental cues.

细胞毒性CD8 ⁺ T细胞在消除细胞内感染和恶性细胞中起关键作用，可提供长期保护性免疫。在对感染的反应中，CD8 ⁺ T 细胞代谢与由细胞外代谢物和免疫信号驱动的转录、翻译和表观遗传变化相关。这些程序促进 CD8 ⁺ T 细胞适应循环和组织中遇到的多样化和动态代谢环境。在疾病的背景下，细胞内在和细胞外的代谢线索都有助于 CD8 ⁺T 细胞功能障碍。此外，全身代谢的变化，无论是通过自愿的还是疾病引起的饮食改变，都会影响 CD8 ⁺ T 细胞介导的免疫。定义 CD8 ⁺ T 细胞在特定组织环境中的代谢适应性有助于我们了解这些细胞如何抵御病原体和肿瘤并维持屏障部位的组织健康。在这里，我们重点介绍了揭示代谢网络如何执行特定 CD8 ⁺ T 细胞程序的最新发现，并讨论了代谢如何与 CD8 ⁺ T 细胞分化和功能结合并由环境因素决定。