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Access through your institution Buy or subscribe Bengsch _et al_. investigated the metabolic changes associated with the development of exhausted CD8+ T cells in mice during a chronic viral
infection compared with metabolic changes in effector CD8+ T cells during an acute viral infection. Developing exhausted T cells were shown to have reduced mitochondrial respiration, and
restricted glucose uptake and glycolysis, with an increased dependency on the residual glycolysis, compared with effector T cells at day 8 post infection. However, these cells had increased
mitochondrial mass, which was surprising given the low mitochondrial energetics in these cells. Further investigations showed that a significantly higher number of developing exhausted T
cells had depolarized and fused mitochondria and increased production of reactive oxygen species (ROS) compare with effector T cells. This suggests that early during a chronic infection,
virus-specific CD8+ T cells display defects in regulating mitochondrial metabolism. Next, the authors examined the signalling pathways underlying defective metabolism in developing exhausted
T cells and found that elevated activity of the metabolic regulator mTOR contributed to the development of the large dysfunctional mitochondria. Furthermore, programmed cell death protein 1
(PD1)-deficient virus-specific CD8+ T cells that were transferred to infected mice showed increased glucose uptake, reduced mitochondrial mass and fewer cells with depolarized mitochondria
compared with controls, which indicates that PD1 has a causal role in establishing the early metabolic dysregulation in developing exhausted T cells. This is a preview of subscription
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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Bengsch, B. et al. Bioenergetic insufficiencies due to metabolic
alterations regulated by coreceptor PD-1 are an early driver of CD8+ T cell exhaustion. _Immunity_ http://dx.doi.org/10.1016/j.immuni.2016.07.008 (2016) * Scharping, N. E. et al. The tumor
microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction. _Immunity_ http://dx.doi.org/10.1016/j.immuni.2016.07.009
(2016) Download references Authors * Olive Leavy View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT
THIS ARTICLE CITE THIS ARTICLE Leavy, O. Defective mitochondria disrupt CD8+ T cells. _Nat Rev Immunol_ 16, 535 (2016). https://doi.org/10.1038/nri.2016.98 Download citation * Published: 25
August 2016 * Issue Date: September 2016 * DOI: https://doi.org/10.1038/nri.2016.98 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get
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