CD8+ T cell expansions and functions rely on glycolysis, but the mechanisms underlying CD8+ T cell glycolytic metabolism remain elusive. Here, we show that acylglycerol kinase (AGK) is required for the establishment and maintenance of CD8+ T cell metabolic and functional fitness. AGK deficiency dampens CD8+ T cell antitumor functions in vivo and perturbs CD8+ T cell proliferation in vitro. Activation of phosphatidylinositol-3-OH kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, which mediates elevated CD8+ T cell glycolysis, is tightly dependent on AGK kinase activity. Mechanistically, T cell antigen receptor (TCR)- and CD28-stimulated recruitment of PTEN to the plasma membrane facilitates AGK-PTEN interaction and AGK-triggered PTEN phosphorylation, thereby restricting PTEN phosphatase activity in CD8+ T cells. Collectively, these results demonstrate that AGK maintains CD8+ T cell metabolic and functional state by restraining PTEN activity and highlight a critical role for AGK in CD8+ T cell metabolic programming and effector function. Hu et al. show a critical role of acylglycerol kinase (AGK) in the establishment and maintenance of CD8+ T cell metabolic and functional fitness. AGK promotes the activation of PI3K-mTOR signaling to mediate CD8+ T cell glycolysis and antitumor functions by restricting PTEN phosphatase activity.
|Original language||English (US)|
|State||Published - Aug 6 2019|
- CD8+ T cells
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology