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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

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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 2

Mitochondrial mass and membrane potential do not differ between healthy control and ME/CFS CD4+ T cells.

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Mitochondrial mass and membrane potential do not differ between healthy ...
(A) MTG, MTR CMXRos, and Hoechst 33342 staining of representative resting and activated control and ME/CFS CD4+ T cells. The experiment was conducted 4 times for each condition. Scale bars: 5 μm. (B) MTG and MTR CMXRos MFI as determined by flow cytometry in healthy control and ME/CFS CD4+ T cells at rest and after overnight activation (n = 15 healthy control samples at rest; n = 14 healthy control samples after activation; n = 17 ME/CFS samples at rest; n = 16 ME/CFS samples after activation). Data represent the mean ± SEM. MTG, MitoTracker Green; MTR, MitoTracker Red.

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