Figure 2.

Metabolic reprogramming in CD8⁺ T‐cell activation and memory formation. (A) Metabolic changes in CD8⁺ T cells upon activation. Upon antigen recognition, stimulatory signals T‐cell receptor (TCR) and costimulation CD28 induce the activation of PI3K‐AKT pathway, mTOR, and the calcium release in the cytosol. This pathway result in the upregulation of the transcription factors NFAT and Myc that promote glycolysis and glutaminolysis. (B) Metabolic regulation during memory CD8⁺ T‐cell formation. After antigen clearance, mTORC1 is inhibited which leads to the downregulation of aerobic glycolysis. Fatty acids are used as main substrates for energy production: fatty acids enter the mitochondria through CPT1‐α and are transformed in acetyl‐CoA by fatty‐acid oxidation. Acetyl‐CoA enters then the tricarboxylic acid cycle to support the oxidative phosphorylation and energy production. Mitochondrial fitness is also closely regulated by proteins involved in mitophagy like Nix and also by inner mitochondrial membrane protein Optic atrophy 1 (OPA1) that promotes mitochondrial fusion.