Vaccine and Infectious Disease Organization (VIDO)-Home of the International Vaccine Centre (InterVac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, S7N 5E3, Canada.
Vaccine and Infectious Disease Organization (VIDO)-Home of the International Vaccine Centre (InterVac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, S7N 5E3, Canada.
Curr Opin Immunol. 2014 Apr;27:60-74. doi: 10.1016/j.coi.2014.01.006. Epub 2014 Feb 18.
Activated T cells undergo metabolic reprogramming which promotes glycolytic flux and lactate production as well as elevated production of lipids, proteins, nucleic acids and other carbohydrates (i.e. induction of biomass) even in the presence of oxygen. Activated T cells show induced expression of, among other things, Glucose Transporter 1 and several glycolytic enzymes, including ADP-Dependent Glucokinase and the low affinity isoform Pyruvate Kinase-M2 (which promote glycolytic flux), as well Glutamine Transporters and Glycerol-3-phosphate Dehydrogenase 2 which make available glutamate and glycerol-3-phosphate as mitochondrial energy sources. Intracellular leucine concentrations critically regulate mammalian target of rapamycin (mTOR) signaling to promote Th1, Th2, and Th17 CD4(+) T effector cell differentiation. In contrast, T regulatory (Treg) cells are generated when AMP-Activating Protein Kinase signaling is activated and mTOR activation is suppressed. Unlike effector CD4(+) and CD8(+) T cells, Tregs and memory T cells oxidize fatty acids for fuel. Effector and memory T cells perform different functions and thus show distinct metabolic profiles which are exquisitely controlled by cellular signaling. Upon activation, T cells express the insulin and leptin receptors on their surface and become sensitive to insulin signaling and nutrient availability and show changes in differentiation. Thus, metabolism and nutrient availability influence T cell activation and function.
活化的 T 细胞经历代谢重编程，即使在有氧气的情况下，也能促进糖酵解通量和乳酸生成，并提高脂质、蛋白质、核酸和其他碳水化合物（即诱导生物量）的产生。活化的 T 细胞表现出葡萄糖转运蛋白 1 和几种糖酵解酶的诱导表达，包括 ADP 依赖性葡萄糖激酶和低亲和力同工型丙酮酸激酶-M2（促进糖酵解通量），以及谷氨酰胺转运蛋白和甘油-3-磷酸脱氢酶 2，它们提供谷氨酸和甘油-3-磷酸作为线粒体能量来源。细胞内亮氨酸浓度严格调节哺乳动物雷帕霉素靶蛋白 (mTOR) 信号，以促进 Th1、Th2 和 Th17 CD4(+)T 效应细胞分化。相比之下，当 AMP 激活蛋白激酶信号被激活且 mTOR 激活被抑制时，会产生调节性 T (Treg) 细胞。与效应 CD4(+)和 CD8(+)T 细胞不同，Treg 和记忆 T 细胞氧化脂肪酸作为燃料。效应和记忆 T 细胞执行不同的功能，因此表现出独特的代谢特征，这些特征受到细胞信号的精细控制。T 细胞在激活后会在其表面表达胰岛素和瘦素受体，并对胰岛素信号和营养物质的可用性变得敏感，并表现出分化的变化。因此，代谢和营养物质的可用性会影响 T 细胞的激活和功能。
