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.
View: Text | PDF
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

×

Figure 5

Basal glycolysis is reduced in ME/CFS CD8+ T cells.

Options: View larger image (or click on image) Download as PowerPoint
Basal glycolysis is reduced in ME/CFS CD8+ T cells. (A) Resting glycolys...
(A) Resting glycolysis measurements from Seahorse extracellular flux analysis of healthy control and ME/CFS CD8+ T cells, including basal glycolysis (n = 21 healthy control samples; n = 20 ME/CFS samples [n = 21/20]), compensatory glycolysis (n = 13/12), and post-2DG acidification (n = 20/18). (B) Glycolysis measurements in stimulated healthy control and ME/CFS CD8+ T cells, including basal glycolysis (n = 14/11), glycolytic capacity (n = 14/11), and post-2DG acidification (n = 13/9). (C) Percentage of GLUT1+ cells in resting and activated CD8+ T cells from patients with ME/CFS and healthy controls (n = 14 healthy control samples at rest; n = 13 healthy control samples after activation; n = 14 ME/CFS samples at rest; n = 14 ME/CFS samples after activation). Box plots represent the median (middle line) and 25th and 75th quartiles (bottom and top edges of box). Whiskers represent 1.5 times the IQR and outliers are defined as values beyond the whiskers. For dot plots, data represent the mean ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001, by Wilcoxon rank-sum test (A and B) and Kruskal-Wallis followed by Dunn’s test with FDR-based multiple testing correction (C).