Figure 2.

The metabolism in senescent and exhausted T cells. Senescent T cells rely more on glycolysis than mitochondrial respiration due to the accumulation of giant non-functional mitochondria in these terminally differentiated cells. The inhibitory receptor KLRG-1 prevents signaling through the TCR, while the activation of p38 blocks autophagy, which senescent T cells use as an energy source. Nonetheless, senescent T cells generate sufficient energy to produce significant amounts of effector cytokine (left). Exhausted T cells express co-inhibitory receptors, which interfere with TCR and co-stimulatory signaling, thereby likely blocking any increase in metabolic activity. Cells may also be prone to mitochondrial induced apoptosis. Additionally, an increase in GAPDH, caused for example by lower levels of glycolysis, might also dampen effector cytokine production (right).