Division of Cell Signalling and Immunology, University of Dundee, Dundee, Scotland, UK.
Eur J Immunol. 2013 Apr;43(4):889-96. doi: 10.1002/eji.201243008. Epub 2013 Feb 13.
The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPKα1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPKα1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPKα1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPKα1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPKα1(null) T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPKα1 monitors energy stress in CTLs and controls CD8 T-cell memory.
腺苷酸单磷酸激活蛋白激酶 (AMPK) 在 T 细胞中被抗原受体信号和能量应激激活。在许多细胞类型中，AMPK 可以维持能量平衡，并通过强制静止来限制能量需求。因此，我们评估了 AMPK 在控制代谢活跃的效应 CD8 T 淋巴细胞向代谢静止的分解代谢记忆 T 细胞过渡中的重要性，这一过程发生在免疫反应的收缩阶段。我们发现，在葡萄糖剥夺引起的代谢应激下，CD8 细胞毒性 T 淋巴细胞（CTL）中的 AMPKα1 迅速激活。此外，在葡萄糖应激条件下，AMPKα1 抑制雷帕霉素复合物 1（mTORC1）的活性。在 CTL 的增殖和分化过程中，AMPKα1 活性并非必需。然而，在免疫刺激停止后，CTL 的体内存活需要 AMPKα1。在李斯特菌感染期间，AMPKα1(null)T 细胞在产生记忆 CD8 T 细胞反应方面也表现出明显缺陷。这些结果表明，AMPKα1 监测 CTL 中的能量应激，并控制 CD8 T 细胞记忆。
