Figure 2.

The Yin-Yang balance of T cell metabolism. Naïve T cells remain quiescent by fully metabolizing the basal amount of glucose into ATP, CO₂ and H₂O through mitochondrial oxidative phosphorylation (OXPHOS). Once exposed to antigen stimulation (e.g., TCR/CD28 signals), naïve T cells rapidly upregulate the uptake of environmental nutrients (e.g., glucose) via activation of the PI3K/AKT/mTOR pathway and switch to aerobic glycolysis to meet the bioenergetic and biosynthesis needs for the clonal expansion and differentiation of antigen-specific effector T cells (Yang side). To prevent T cell overactivation, Tregs are activated by the AMPK/FAO pathway to suppress effector T cell proliferation during the process (Yin side). Upon antigen clearance, activated T cells can develop into memory T cells, which adopt similar FAO metabolism to maintain their long-term survival. The Yin-Yang balance model of T cell metabolism coined here not only describes the functional and metabolic complements of individual T cell subsets, but also help to explain the overall homeostasis and harmony of T cell responses in vivo as a whole.