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2018 ; 96
(6
): 666-674
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Human MAIT cells show metabolic quiescence with rapid glucose-dependent
upregulation of granzyme B upon stimulation
#MMPMID29423939
Zinser ME
; Highton AJ
; Kurioka A
; Kronsteiner B
; Hagel J
; Leng T
; Marchi E
; Phetsouphanh C
; Willberg CB
; Dunachie SJ
; Klenerman P
Immunol Cell Biol
2018[Jul]; 96
(6
): 666-674
PMID29423939
show ga
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.
|Glucose/metabolism
[MESH]
|Granzymes/*metabolism
[MESH]
|Humans
[MESH]
|Lymphocyte Activation/*immunology
[MESH]
|Mucosal-Associated Invariant T Cells/*immunology/*metabolism
[MESH]
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