Figure 1. T Cells Undergo Metabolic Rewiring in Different Stages of Their Life.

(A) Naïve T cells uptake sufficient amounts of glucose to fuel oxidative phosphorylation and survive as they survey antigens. (B) Upon encountering cognate antigen, activated T cells rapidly uptake glucose and glutamine to fuel their bioenergetic needs. Activated T cells perform aerobic glycolysis, which shunts products of glycolysis to biosynthetic processes necessary for proliferation and effector function and generates lactate as a byproduct. (C) Once the antigen is cleared, T cells can form long-lived memory cells in which AMPK signaling stimulates fatty acid oxidation. Memory T cells also increase their mitochondrial mass and spare respiratory capacity to prepare for future encounter with cognate antigen. (D) T cells can become exhausted if they fail to clear antigens such as during chronic infections or cancer. T lymphocytes isolated from tumors display elevated levels of PD-1, which decreases PI3K/Akt/mTOR signaling and glycolysis. Exhausted TILs rely on fatty acid oxidation, though they often have dysfunctional mitochondria and decreased mitochondrial mass as well.