Human MAIT cells show metabolic quiescence with rapid glucose-dependent upregulation of granzyme B upon stimulation

Immunol Cell Biol. 2018 Jul;96(6):666-674. doi: 10.1111/imcb.12020. Epub 2018 Mar 9.


Mucosal-associated invariant T (MAIT) cells are a well-characterized innate-like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial metabolites presented on MR1, and through cytokine-mediated triggering. Typically, they show a quiescent memory phenotype but can undergo rapid upregulation of effector functions including cytolysis upon stimulation. T cells profoundly change their cellular metabolism during their maturation and activation. We sought to determine how MAIT cell metabolism may facilitate both the long-term memory phase in tissue and the transition to rapid effector function. Here, we show, by flow cytometric metabolism assays and extracellular flux analysis that, despite an effector-memory profile, human MAIT cells are metabolically quiescent in a resting state comparable to naïve and central memory T cells. Upon stimulation, they rapidly increase uptake of glucose and show a concomitant upregulation of the effector molecules notably granzyme B, which is impaired by inhibition of glycolysis with 2-deoxyglucose. These findings suggest that MAIT cells share some metabolic characteristics of both resting and effector T cell subsets, with a rapid transition upon triggering. Metabolic programming of this cell type may be of interest in understanding and modulating their function in infectious diseases and cancer.

Keywords: MAIT cells; T cells; metabolism; mucosal immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glucose / metabolism
  • Granzymes / metabolism*
  • Humans
  • Lymphocyte Activation / immunology*
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism*
  • Up-Regulation


  • GZMB protein, human
  • Granzymes
  • Glucose