Metabolic reprogramming of t-lymphocytes during immune activation: Glycolytic switch and its implications for effector function

Abstract

T-lymphocyte activation triggers dramatic metabolic reprogramming from oxidative phosphorylation toward aerobic glycolysis, supporting rapid proliferation and effector function. This research characterized the glycolytic switch in human CD4+ and CD8+ T cells following activation. Experiments at Accra Institute of Technology from February 2024 to June 2025 employed extracellular flux analysis and metabolite profiling in primary human T cells stimulated through CD3/CD28. Results showed glycolytic rate increased 8.4-fold within 24 hours of activation, with glucose uptake rising 5.2-fold. GLUT1 surface expression increased 4.8-fold while hexokinase II protein levels rose 3.6-fold. Inhibiting glycolysis with 2-deoxyglucose reduced IFN-γ production by 67% and proliferation by 78%. These findings demonstrate the essential role of metabolic reprogramming in T cell effector responses with implications for immunotherapy and autoimmune disease treatment.