The study’s authors knew the immune system was dysregulated in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) but wondered which parts shift with the condition. A systematic exploration revealed that key CD8+ T cells displayed one of the most pronounced signatures of dysregulation, with signs of constant stimulation that lead to an exhausted state, a condition that is well-studied in cancer.

“This is an important finding for ME/CFS because now we can examine the T cells more carefully, and hopefully by looking in the exhausted cells we can start to get hints as to what they are responding to,” said Andrew Grimson, professor of molecular biology and co-corresponding author of the study. Maureen Hanson, professor of molecular biology and genetics, is the other corresponding author.

“Therapies have been developed to reverse T cell exhaustion as treatments for cancer,” Hanson said. “Our findings raise the question of whether such anti-exhaustion drugs might also be helpful in ME/CFS.”

Strong evidence for the phenomenon of T cell exhaustion in ME/CFS has also been reported in long COVID, Hanson added.

“Immune cells from ME/CFS patients exhibited higher levels of proteins on their surface that are characteristic of cells that have become exhausted, which can be caused by long-term exposure to a virus protein or by continuous stimulation of the immune system, a state that is also found in cancer patients,” Hanson said.

Future work will try to determine whether a virus is in fact involved, which is currently not known. “We need to understand what is pushing them to this exhausted state,” Grimson said.

The team also plans to take cells from patients and controls, purify those cells and treat patients with drugs that reverse exhaustion and see if the immune cells resume normal function. If CD8+ T cell exhaustion can be reversed, the next question is whether such reversal actually benefits a patient, as exhaustion can have protective qualities.