According to a new Cornell University study, chronic fatigue syndrome creates conditions where pathogen-killing immune T cells become exhausted.
The study’s authors were aware that the immune system is dysregulated in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Still, they sought to identify which specific components were affected by the condition. Through a systematic exploration, they discovered that key CD8+ T cells exhibited one of the most significant signs of dysregulation. These cells showed evidence of continuous stimulation, which ultimately leads to an exhausted state—a phenomenon that has been extensively studied in cancer.
“This is an important discovery for ME/CFS because it allows us to examine T cells more closely. By investigating the exhausted cells, we hope to gain insights into what they are responding to,” said Andrew Grimson, a professor of molecular biology and co-corresponding author of the study. Maureen Hanson, a molecular biology and genetics professor, is the corresponding author.
“Therapies have been developed to reverse T cell exhaustion as treatments for cancer,” Hanson stated. “Our findings raise the question of whether these anti-exhaustion drugs could also be beneficial for ME/CFS.”
Hanson added that there is strong evidence for T cell exhaustion in ME/CFS, which has also been observed in long COVID.
“According to Hanson, immune cells from patients with ME/CFS showed elevated levels of surface proteins that are typical of exhausted cells. This exhaustion can result from prolonged exposure to a viral protein or ongoing stimulation of the immune system, a condition also observed in cancer patients.”
Future work will try to determine whether a virus is 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, 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 benefits a patient, as exhaustion can have protective qualities.