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Immune cell metabolism altered in ME/CFS

Colorized scanning electron micrograph of a T cell. The study focused on T cells in people with ME/CFS. NIAID

ME/CFS is a complex, poorly understood disease. Symptoms can include fatigue, chronic pain, problems thinking and concentrating, poor sleep, and gut problems. These symptoms often worsen after physical or mental activity that wouldn’t have caused a problem before the illness. This is known as post-exertional malaise.

About a quarter of people with ME/CFS become house- or bed-bound at some point. Scientists don’t know what causes the disease. This has prevented the development of effective treatments.

Whether or not specific microbes—such as a virus—may play a role in ME/CFS is not well understood. Recent research suggests that the immune system is involved in ME/CFS. In particular, researchers are interested in metabolism—how energy is produced and used—within immune cells.

To look more closely at immune-cell metabolism in ME/CFS, researchers led by Drs. Alexandra Mandarano and Maureen Hanson at Cornell University collected blood samples from 53 people with ME/CFS and 45 people without the disease. They tested specific types of immune cells in the blood for changes in metabolism, both at rest and after being activated by signals that indicate a danger to the body.

The team focused on CD4+ and CD8+ T cells. CD4+ T cells alert other immune cells about invading pathogens. CD8+ T cells attack infected cells in the body. The study was funded in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Allergy and Infectious Diseases (NIAID). Results were published on December 12, 2019, in the Journal of Clinical Investigation.

Most aspects of immune-cell metabolism measured by the researchers did not differ between samples taken from people with ME/CFS and those without the disease. But there were exceptions.

CD8+ T cells from people with ME/CFS showed a decrease in energy production after activation. Notably, they had changes in their mitochondria—the structures that produce most of the cell’s energy.

Compared to cells taken from people without the disease, both CD4+ and CD8+ cells from people with ME/CFS had reduced glycolosis at rest. Glycolosis is another pathway that cells use to produce energy. CD8+ cells from people with ME/CFS also had reduced glycolysis after activation.

The team found different patterns of cytokines in the blood of people with ME/CFS as well. Cytokines play important signaling roles in the immune system. Although many of these cytokines would normally promote immune activity, they correlated with reduced metabolism in CD8+ T cells in people with the disease.

More work is needed to understand whether altered cytokine production and reduced T-cell metabolism play a role in ME/CSF. “Additional studies focusing on specific cell types will be important to unravel what’s gone wrong with immune defenses in ME/CFS,” Hanson says.