Researchers at UC San Francisco have uncovered a new clue to how Epstein-Barr virus (EBV) could contribute to multiple sclerosis (MS), a chronic autoimmune disease that affects nearly one million Americans.
The study , published Feb. 5 in Nature Immunology, found that certain types of CD8+ “killer” T cells — immune cells that destroy damaged or infected cells — are more abundant in people with MS. Some of these killer T cells target EBV, which suggests that the virus may trigger the damaging immune response seen in MS.
Scientists have known for several years that EBV — a common virus carried by about 95% of adults — is present in virtually everyone who develops MS.
“Looking at these understudied CD8+ T cells connects a lot of different dots and gives us a new window on how EBV is likely contributing to this disease,” said senior author Joe Sabatino , MD, PhD, an assistant professor of Neurology who is a member of the UCSF Weill Institute for Neurosciences .
MS develops when the immune system mistakenly attacks the myelin that coats nerve fibers in the brain and spinal cord, leading to progressive neurological damage. Until now, most MS research has focused on CD4+ T cells, which coordinate immune responses but do not directly kill cells. CD4+ T cells are easier to study in animal models of MS than CD8+ killer T cells.
Sabatino’s team decided to examine the killer T cells directly in people. They analyzed blood and cerebrospinal fluid (CSF) from 13 patients with MS or early signs of the disease, as well as five people without MS.
The researchers looked at CD8+ T cells that recognized specific proteins in each of these fluids.
In the study participants without MS, the cells that recognized these proteins were similarly abundant in the blood and CSF. But in the participants with MS, these cells were between 10 and 100 times more abundant in the CSF than in the blood. This huge difference indicated that something unusual must be happening in the central nervous system — and that the immune cells were responding to it.
The Epstein-Barr virus was also present in the CSF of most study participants, whether or not they had MS, and some of its genes were active. One of these genes was only active in people with MS, which suggests that it may be driving the overactive immune response characteristic of MS.
The findings are just the latest to implicate EBV in autoimmune disease. Along with MS, the virus has been linked to lupus, rheumatoid arthritis, and long COVID.
Some MS researchers have already begun testing therapies that target EBV.
“The big hope here is that if we can interfere with EBV, we can have a big effect, not just on MS but on other disorders, and improve the quality of life for many, many people,” Sabatino said.
Authors: Additional UCSF authors on the study include Fumie Hayashi, Kristen Mittl, Ravi Dandekar, Josiah Gerdts, Ebtesam Hassan, Ryan D. Schubert, Lindsay Oshiro, Rita Loudermilk, Ariele Greenfield, Danillo G. Augusto, Gregory Havton, Shriya Anumarlu, Arhan Surapaneni, Akshaya Ramesh, Edwina Tran, Kanishka Koshal, Kerry Kizer, Isabelle J. Fisher, Tiffany Cooper, Meagan Harms, Refujia Gomez, University of California, San Francisco MS-EPIC Team, Claire D. Clelland, Bruce A. C. Cree, Stephen L. Hauser, Jill A. Hollenbach, Michael R. Wilson, and Scott S. Zamvil. For other authors, please see the study.
Funding: The study was funded by the National Institutes of Health (grants K08NS107619, R01AI158861, R01AI169070, R01AI169070, R35NS111644, and R21AI142186)
About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health , which serves as UCSF’s primary academic medical center, includes among the nation's top specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno. Learn more at ucsf.edu or see our Fact Sheet .
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Nature Immunology