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

Nat Immunol. 2013 Oct;14(10):1064-72. doi: 10.1038/ni.2687. Epub 2013 Aug 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Chromatin Assembly and Disassembly
  • Epitopes, T-Lymphocyte / immunology
  • Glycolysis
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Lymphocyte Activation
  • Mechanistic Target of Rapamycin Complex 2
  • Metabolome
  • Metabolomics
  • Multiprotein Complexes / metabolism
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism


  • Epitopes, T-Lymphocyte
  • Multiprotein Complexes
  • Interferon-gamma
  • Mechanistic Target of Rapamycin Complex 2
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases