Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host

Cell Rep. 2016 Aug 2;16(5):1243-1252. doi: 10.1016/j.celrep.2016.06.078. Epub 2016 Jul 21.


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.

MeSH terms

  • Adolescent
  • Adult
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / virology*
  • Cytomegalovirus / pathogenicity
  • Female
  • Glucose / metabolism
  • Glucose Transporter Type 1 / metabolism
  • Glycolysis / physiology
  • Hepatitis B virus / pathogenicity
  • Humans
  • Interleukin-12 / metabolism
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Mitochondria / virology
  • Oxidative Phosphorylation
  • Programmed Cell Death 1 Receptor / metabolism
  • Virus Diseases / metabolism
  • Virus Diseases / physiopathology
  • Virus Diseases / virology
  • Young Adult


  • Glucose Transporter Type 1
  • Programmed Cell Death 1 Receptor
  • Interleukin-12
  • Glucose