Division of Biological Sciences, Section of Molecular Biology, University of California, San Diego, La Jolla, CA, USA.
Nat Rev Immunol. 2021 Nov;21(11):718-738. doi: 10.1038/s41577-021-00537-8. Epub 2021 May 12.
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 细胞在清除细胞内感染和恶性细胞方面发挥着关键作用,并且可以提供长期的保护性免疫。在对感染的反应中,CD8 T 细胞的代谢与转录、翻译和表观遗传变化相偶联,这些变化是由细胞外代谢物和免疫信号驱动的。这些程序促进了 CD8 T 细胞适应在循环和组织中遇到的多样化和动态代谢环境。在疾病情况下,细胞内和细胞外的代谢线索都导致 CD8 T 细胞功能障碍。此外,全身代谢的变化,无论是通过自愿还是疾病引起的饮食改变,都可以影响 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,使我们能够了解这些细胞如何抵抗病原体和肿瘤,并维持屏障部位的组织健康。在这里,我们强调了最近的发现,这些发现揭示了代谢网络如何强制实施特定的 CD8 T 细胞程序,并讨论了代谢如何与 CD8 T 细胞分化和功能相整合,并受环境线索的影响。