Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations

J Clin Invest. 2020 Mar 2;130(3):1491-1505. doi: 10.1172/JCI132185.


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease with no known cause or mechanism. There is an increasing appreciation for the role of immune and metabolic dysfunction in the disease. ME/CFS has historically presented in outbreaks, often has a flu-like onset, and results in inflammatory symptoms. Patients suffer from severe fatigue and postexertional malaise. There is little known about the metabolism of specific immune cells in patients with ME/CFS. To investigate immune metabolism in ME/CFS, we isolated CD4+ and CD8+ T cells from 53 patients with ME/CFS and 45 healthy controls. We analyzed glycolysis and mitochondrial respiration in resting and activated T cells, along with markers related to cellular metabolism and plasma cytokines. We found that ME/CFS CD8+ T cells had reduced mitochondrial membrane potential compared with those from healthy controls. Both CD4+ and CD8+ T cells from patients with ME/CFS had reduced glycolysis at rest, whereas CD8+ T cells also had reduced glycolysis following activation. Patients with ME/CFS had significant correlations between measures of T cell metabolism and plasma cytokine abundance that differed from correlations seen in healthy control subjects. Our data indicate that patients have impaired T cell metabolism consistent with ongoing immune alterations in ME/CFS that may illuminate the mechanism behind this disease.

Keywords: Glucose metabolism; Immunology; Metabolism; Mitochondria; T cells.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / metabolism
  • CD4-Positive T-Lymphocytes* / pathology
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • CD8-Positive T-Lymphocytes* / pathology
  • Cytokines* / blood
  • Cytokines* / immunology
  • Fatigue Syndrome, Chronic* / blood
  • Fatigue Syndrome, Chronic* / immunology
  • Fatigue Syndrome, Chronic* / pathology
  • Female
  • Glycolysis / immunology
  • Humans
  • Male
  • Middle Aged
  • Mitochondria* / immunology
  • Mitochondria* / metabolism
  • Mitochondria* / pathology
  • Oxygen Consumption / immunology


  • Cytokines