Sensitivity to Restimulation-Induced Cell Death Is Linked to Glycolytic Metabolism in Human T Cells.

ABSTRACT: 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 c

SUBMITTER: Larsen SE 

PROVIDER: S-EPMC5310646 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature