Human MAIT cells show metabolic quiescence with rapid glucose‐dependent upregulation of granzyme B upon stimulation. Issue 6 (9th March 2018)

• Record Type: Journal Article
• Authors: Zinser, Madeleine E; Highton, Andrew J; Kurioka, Ayako; Kronsteiner, Barbara; Hagel, Joachim; Leng, Tianqi; Marchi, Emanuele; Phetsouphanh, Chansavath; Willberg, Chris B; Dunachie, Susanna J; Klenerman, Paul
• Is Part Of: Immunology and cell biology. Volume 96:Issue 6(2018)
• Page Start: 666
• Page End: 674
• Publication Date: 2018-03-09
• Subjects: MAIT cells -- metabolism -- mucosal immunology -- T cells; Immunology -- Periodicals; Cytology -- Periodicals; 616.079
• DOI: 10.1111/imcb.12020
• Languages: English
• ISSNs: 0818-9641

Abstract

Abstract: 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. Abstract : Mucosal‐associated invariant T (MAIT) cells are an innate‐like T cell population abundant in humans. T cell immunometabolism has been studied before in memory cell populations showing distinct usage of metabolic pathways according to activation status. Here, we show for the first time that upon stimulation, MAIT cells engage their glycolytic pathway along with an upregulation of the effector molecule granzyme B. See also: Special Feature on MAIT cells