Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells

Eur J Immunol. 2008 Sep;38(9):2438-50. doi: 10.1002/eji.200838289.


We recently reported that differentiation of CD8(+) T cells from the naïve to the effector state involves the upregulation of glucose-dependent metabolism. Glucose deprivation or inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) selectively inhibited production of IFN-gamma but not of IL-2. To determine a more global role of glucose metabolism on effector T-cell function, we performed gene array analysis on CD8(+) effector T cells stimulated in the presence or absence of 2-DG. We observed that expression of only 10% of genes induced by TCR/CD28 signaling was inhibited by 2-DG. Among these were genes for key cytokines, cell cycle molecules, and cytotoxic granule proteins. Consistent with these results, production of IFN-gamma and GM-CSF, cell cycle progression, upregulation of cyclin D2 protein, cytolytic activity, and upregulation of granzyme B protein and also conjugate formation were exquisitely glucose-dependent. In contrast to glucose, oxygen was little utilized by CD8(+) effector T cells, and relative oxygen deprivation did not inhibit these CTL functional properties. Our results indicate a particularly critical role for glucose in regulating specific effector functions of CD8(+) T cells and have implications for the maintenance of the effector phase of cellular immune responses in target tissue microenvironments such as a solid tumor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cytokines / biosynthesis*
  • Cytokines / immunology
  • Cytotoxicity, Immunologic*
  • Deoxyglucose / pharmacology
  • Gene Expression Profiling
  • Gene Expression*
  • Glucose / metabolism*
  • Lymphocyte Activation*
  • Mice
  • Oxygen / metabolism


  • Cytokines
  • Deoxyglucose
  • Glucose
  • Oxygen