Affected T cells show (i) deficits in basal glycolysis that may interplay with (ii) abnormalities in mitochondrial metabolism, with decreased proton leak at rest and reduced ATP production in the CD8⁺ subset upon activation. (iii) Resting and activated CD8⁺ cells also show decreased mitochondrial membrane potential, and a resting CD8⁺ subset may display increased mitochondrial mass. Alterations in factors that have been previously shown (red) suggest that deficits in bioenergetics, metabolic reprogramming, and mitochondrial dynamics may vary across more specific CD4⁺ and CD8⁺ T cell subsets, including subsets with features of immune aging, senescence, or exhaustion (3, 4, 7–10, 15, 16). FAO, fatty acid oxidation; MAVS, mitochondrial antiviral signaling protein; mtROS, mitochondrial reactive oxygen species; NAD⁺, nicotinamide adenine dinucleotide; NLRP3, NOD-, LRR- and pyrin domain–containing protein 3 (inflammasome); OXPHOS, oxidative phosphorylation; RIG-I, retinoic acid–inducible gene I; SIRT3, NAD-dependent deacetylase sirtuin-3; TCA, tricarboxylic acid cycle; TGF-β, transforming growth factor β; Trp, tryptophan.