Ketolysis drives CD8⁺ T cell effector function through effects on histone acetylation.

ABSTRACT: Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)-including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)-as essential fuels supporting CD8⁺ T cell metabolism and effector function. βOHB directly increased CD8⁺ T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge. CD8⁺ Teff cells preferentially used KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boosted the respiratory capacity and TCA cycle-dependent metabolic pathways that fuel CD8⁺ T cell function. Mechanistically

SUBMITTER: Luda KM 

PROVIDER: S-EPMC10528215 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature