期刊
Cell Reports
卷 16, 期 5, 页码 1243-1252出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.06.078
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资金
- Wellcome Trust
- MRC Project [MR/M020126/]
- EASL
- Barts and The London Charity
- UCLH CIDC/NIHR Fast Track Grant
- Wolfson Foundation
- Wellcome Trust [101849/Z/13/Z] Funding Source: Wellcome Trust
- MRC [MR/M020126/1, MC_UU_12022/6] Funding Source: UKRI
- Medical Research Council [MC_UU_12022/6, MR/M020126/1] Funding Source: researchfish
- Wellcome Trust [101849/Z/13/Z] Funding Source: researchfish
T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1(hi) T cell response against hepatitis B virus (HBV) had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1 hi HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV)-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL)-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells.
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