Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells
Open Access
- 15 September 2008
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 38 (9), 2438-2450
- https://doi.org/10.1002/eji.200838289
Abstract
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‐γ 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‐γ 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.Keywords
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