title: Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch.
abstract: Antigen-experienced memory T cells acquire effector function with innate-like kinetics; however, the metabolic requirements of these cells are unknown. Here we show that rapid interferon-γ (IFN-γ) production of effector memory (EM) CD8(+) T cells, activated through stimulation mediated by the T cell antigen receptor (TCR) and the costimulatory receptor CD28 or through cognate interactions, was linked to increased glycolytic flux. EM CD8(+) T cells exhibited more glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity at early time points, before proliferation commenced, than did naive cells activated under similar conditions. CD28 signaling via the serine-threonine kinase Akt and the metabolic-checkpoint kinase mTORC2 was needed to sustain TCR-mediated immediate-early glycolysis. Unlike glycolysis in proliferating cells, immediate-early glycolysis in memory CD8(+) T cells was rapamycin insensitive. Thus, CD8(+) memory T cells have an Akt-dependent 'imprinted' glycolytic potential that is required for efficient immediate-early IFN-γ recall responses.
authors: 1] Department of Biomedicine, Immunobiology, University of Basel, Basel, Switzerland. [2].
authors: Patrick M
authors: PM
authors: Gubser
authors: Glenn R
authors: GR
authors: Bantug
authors: Leyla
authors: L
authors: Razik
authors: Marco
authors: M
authors: Fischer
authors: Sarah
authors: S
authors: Dimeloe
authors: Gideon
authors: G
authors: Hoenger
authors: Bojana
authors: B
authors: Durovic
authors: Annaïse
authors: A
authors: Jauch
authors: Christoph
authors: C
authors: Hess
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006019:Glycolysis; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D000076225:Mechanistic Target of Rapamycin Complex 2; D055442:Metabolome; D055432:Metabolomics; D046912:Multiprotein Complexes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D046912:Multiprotein Complexes; D007371:Interferon-gamma; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
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