Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations
Alexandra H. Mandarano, … , C. Gunnar Gottschalk, Maureen R. Hanson
Alexandra H. Mandarano, … , C. Gunnar Gottschalk, Maureen R. Hanson
Published December 12, 2019
Citation Information: J Clin Invest. 2020;130(3):1491-1505. https://doi.org/10.1172/JCI132185.
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Research Article Immunology Metabolism

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

Abstract

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.

Authors

Alexandra H. Mandarano, Jessica Maya, Ludovic Giloteaux, Daniel L. Peterson, Marco Maynard, C. Gunnar Gottschalk, Maureen R. Hanson

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Figure 6

Plasma cytokines are uniquely correlated with T cell metabolism in patients with ME/CFS.

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Plasma cytokines are uniquely correlated with T cell metabolism in patie...
Significant correlations between plasma cytokines and cellular metabolism in patients and nonsignificant correlations in healthy controls. Correlations between resting CD8+ T cell (CD8+ T) basal glycolysis and (A) IL-2 (n = 19 patients; n = 21 controls), (B) IL-8 (n = 18 patients; n = 19 controls), (C) IL-10 (n = 19 patients; n = 21 controls), (D) IL-12 p70 (n = 19 patients; n = 21 controls), (E) SCGF-β (n = 19 patients; n = 20 controls), (F) and IL-9 (n = 19 patients; n = 21 controls); between resting CD8+ T cell compensatory glycolysis and (G) M-CSF (n = 12 patients; n = 12 controls) and (H) TNF-α (n = 12 patients; n = 12 controls); (I) between activated CD8+ T cell post-2DG acidification and M-CSF (n = 9 patients; n = 13 controls); and (J) between activated CD8+ T cell glycolytic capacity and M-CSF (n = 10 patients; n = 14 controls). All correlations were evaluated using a Spearman’s correlation test with FDR-based multiple testing correction, where a q value of less than 0.01 was considered significant.