Trudeau Institute, Saranac Lake, NY 12983, USA.
Immunity. 2012 Jan 27;36(1):68-78. doi: 10.1016/j.immuni.2011.12.007. Epub 2011 Dec 28.
CD8(+) T cells undergo major metabolic changes upon activation, but how metabolism influences the establishment of long-lived memory T cells after infection remains a key question. We have shown here that CD8(+) memory T cells, but not CD8(+) T effector (Teff) cells, possessed substantial mitochondrial spare respiratory capacity (SRC). SRC is the extra capacity available in cells to produce energy in response to increased stress or work and as such is associated with cellular survival. We found that interleukin-15 (IL-15), a cytokine critical for CD8(+) memory T cells, regulated SRC and oxidative metabolism by promoting mitochondrial biogenesis and expression of carnitine palmitoyl transferase (CPT1a), a metabolic enzyme that controls the rate-limiting step to mitochondrial fatty acid oxidation (FAO). These results show how cytokines control the bioenergetic stability of memory T cells after infection by regulating mitochondrial metabolism.
CD8(+) T 细胞在激活后会经历重大的代谢变化，但代谢如何影响感染后产生长寿的记忆 T 细胞仍然是一个关键问题。我们在这里表明，CD8(+)记忆 T 细胞，而不是 CD8(+)T 效应（Teff）细胞，具有大量的线粒体备用呼吸能力（SRC）。SRC 是细胞在应对增加的应激或工作时产生能量的额外能力，因此与细胞存活相关。我们发现白细胞介素-15（IL-15），一种对 CD8(+)记忆 T 细胞至关重要的细胞因子，通过促进线粒体生物发生和肉毒碱棕榈酰转移酶（CPT1a）的表达来调节 SRC 和氧化代谢，CPT1a 是一种控制线粒体脂肪酸氧化（FAO）限速步骤的代谢酶。这些结果表明细胞因子如何通过调节线粒体代谢来控制感染后记忆 T 细胞的生物能量稳定性。
