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Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch

Gubser, P. M. and Bantug, G. R. and Razik, L. and Fischer, M. and Dimeloe, S. and Hoenger, G. and Durovic, B. and Jauch, A. and Hess, C.. (2013) Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch. Nature immunology, Vol. 14, H. 10. pp. 1064-1072.

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Official URL: http://edoc.unibas.ch/dok/A6338507

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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-gamma (IFN-gamma) 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-gamma recall responses.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immunobiology (Hess C)
UniBasel Contributors:Hess, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature America
ISSN:1529-2908
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:12
Deposited On:10 Apr 2015 09:12

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