Sensitivity to Restimulation-Induced Cell Death Is Linked to Glycolytic Metabolism in Human T Cells.
Sasha E LarsenAbegail BilenkinTatiana N TarasenkoSwadhinya ArjunarajaJeffrey R StinsonPeter J McGuireAndrew L SnowPublished in: Journal of immunology (Baltimore, Md. : 1950) (2016)
Restimulation-induced cell death (RICD) regulates immune responses by restraining effector T cell expansion and limiting nonspecific damage to the host. RICD is triggered by re-engagement of the TCR on a cycling effector T cell, resulting in apoptosis. It remains unclear how RICD sensitivity is calibrated in T cells derived from different individuals or subsets. In this study we show that aerobic glycolysis strongly correlates with RICD sensitivity in human CD8+ effector T cells. Reducing glycolytic activity or glucose availability rendered effector T cells significantly less sensitive to RICD. We found that active glycolysis specifically facilitates the induction of proapoptotic Fas ligand upon TCR restimulation, accounting for enhanced RICD sensitivity in highly glycolytic T cells. Collectively, these data indicate that RICD susceptibility is linked to metabolic reprogramming, and that switching back to metabolic quiescence may help shield T cells from RICD as they transition into the memory pool.
Keyphrases
- regulatory t cells
- cell death
- endothelial cells
- dendritic cells
- high glucose
- cell cycle arrest
- immune response
- type iii
- oxidative stress
- diabetic rats
- induced pluripotent stem cells
- drug induced
- high intensity
- working memory
- pluripotent stem cells
- electronic health record
- metabolic syndrome
- type diabetes
- toll like receptor
- endoplasmic reticulum stress
- deep learning
- weight loss
- insulin resistance
- data analysis