近日，英国邓迪大学教授Doreen A. Cantrell及其小组报道了抗原和细胞因子抑制自噬影响CD8 T细胞的线粒体、迁移和效应机制细胞。该项研究成果发表在2025年2月27日出版的《自然—免疫学》上。

在此，课题组人员证明幼稚CD8 T细胞具有较高的自噬通量，课题组人员确定了一个自噬检查点，抗原受体参与和炎症细胞因子通过调节氨基酸转运蛋白表达和细胞内氨基酸递送来急性抑制自噬。激活具有高水平氨基酸转运体的T细胞在氨基酸充足的条件下自噬通量低，但当氨基酸受到限制时，细胞会迅速恢复自噬。一项对自噬降解和促进的蛋白质的调查显示，自噬如何塑造CD8 T细胞蛋白质组。在细胞毒性T细胞中，主要的自噬底物包括细胞溶解效应分子、氨基酸和葡萄糖转运体。在朴素T细胞中，线粒体自噬占主导地位，选择性线粒体修剪支持协调T细胞迁移和存活。自噬它们会对初始和效应T进行不同的修剪由抗原受体和炎性细胞因子动态抑制形成T细胞分化。

研究人员表示，自噬塑造CD8 T细胞的命运;然而，这一进程的时机、触发因素和目标都没有明确定义。

附：英文原文

Title: Autophagy repression by antigen and cytokines shapes mitochondrial, migration and effector machinery in CD8 Tcells

Author: Sinclair, Linda V., Youdale, Tom, Spinelli, Laura, Gakovic, Milica, Langlands, Alistair J., Pathak, Shalini, Howden, Andrew J. M., Ganley, Ian G., Cantrell, Doreen A.

Issue&Volume: 2025-02-27

Abstract: Autophagy shapes CD8 Tcell fate; yet the timing, triggers and targets of this process are poorly defined. Herein, we show that naive CD8 Tcells have high autophagic flux, and we identify an autophagy checkpoint whereby antigen receptor engagement and inflammatory cytokines acutely repress autophagy by regulating amino acid transporter expression and intracellular amino acid delivery. Activated Tcells with high levels of amino acid transporters have low autophagic flux in amino-acid-replete conditions but rapidly reinduce autophagy when amino acids are restricted. A census of proteins degraded and fueled by autophagy shows how autophagy shapes CD8 Tcell proteomes. In cytotoxic Tcells, dominant autophagy substrates include cytolytic effector molecules, and amino acid and glucose transporters. In naive Tcells, mitophagy dominates and selective mitochondrial pruning supports the expression of molecules that coordinate Tcell migration and survival. Autophagy thus differentially prunes naive and effector Tcell proteomes and is dynamically repressed by antigen receptors and inflammatory cytokines to shape Tcell differentiation.

DOI: 10.1038/s41590-025-02090-1

Source: https://www.nature.com/articles/s41590-025-02090-1