[PDF][PDF] Distinct metabolic requirements of exhausted and functional virus-specific CD8 T cells in the same host

A Schurich, LJ Pallett, D Jajbhay, J Wijngaarden… - Cell reports, 2016 - cell.com
A Schurich, LJ Pallett, D Jajbhay, J Wijngaarden, I Otano, US Gill, N Hansi, PT Kennedy…
Cell reports, 2016cell.com
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 …
Summary
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-1hi 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. Glut1hi 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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