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

• Published in: The Journal of clinical investigation Vol. 130; no. 3; pp. 1491 - 1505
• Main Authors: Mandarano, Alexandra H., Maya, Jessica, Giloteaux, Ludovic, Peterson, Daniel L., Maynard, Marco, Gottschalk, C. Gunnar, Hanson, Maureen R.
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.03.2020
• Subjects: Analysis; Biomedical research; CD4 antigen; CD8 antigen; Chronic fatigue syndrome; Cytokines; Cytotoxicity; Disease; Diseases; Encephalomyelitis; Exhibitions; Fatigue; Fatty acids; Glucose metabolism; Glycolysis; Illnesses; Immune system; Infections; Inflammation; Influenza; Instrument industry (Equipment); Lymphocytes; Lymphocytes T; Medical research; Membrane potential; Metabolism; Metabolites; Mitochondria; Pathogens; Patients; Physiological aspects; Plasma; Respiration; Studies; T cells; Viral infections; United States; United States > US; Nevada; Glucose metabolism; Mitochondria; Immunology; Metabolism; T cells
• ISSN: 0021-9738; 1558-8238; 1558-8238
• 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.