Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations, by Alexandra H Mandarano, Jessica Maya, Ludovic Giloteaux, Daniel L Peterson, Marco Maynard, C Gunnar Gottschalk, and Maureen R Hanson in J Clin Invest. 2019. [First published December 12, 2019] https://doi.org/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 post-exertional malaise. There is little known about the metabolism of specific immune cells in ME/CFS patients.
To investigate immune metabolism in ME/CFS, we isolated CD4+ and CD8+ T cells from 53 ME/CFS patients 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 have reduced mitochondrial membrane potential compared to healthy controls. Both CD4+ and CD8+ T cells from ME/CFS patients had reduced glycolysis at rest, while CD8+ T cells also had reduced glycolysis following activation. ME/CFS patients had significant correlations between measures of T cell metabolism and plasma cytokine abundance that differed from 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.
NIH press release: Study finds differences in energy use by immune
cells in ME/CFS
Dr. Hanson and her colleagues did not see significant differences in mitochondrial respiration, the cell’s primary energy-producing method, between healthy and ME/CFS cells at rest or after activation. However, results suggest that glycolysis, a less efficient method of energy production, may be disrupted in ME/CFS. Compared to healthy cells, CD4 and CD8 cells from people with ME/CFS had decreased levels of glycolysis at rest. In addition, ME/CFS CD8 cells had lower levels of glycolysis after activation.
“Our work demonstrates the importance of looking at particular types of immune cells that have different jobs to do, rather than looking at them all mixed together, which can hide problems specific to particular cells,” said Dr. Hanson. “Additional studies focusing on specific cell types will be important to unravel what’s gone wrong with immune defenses in ME/CFS.”