A new study reveals how Epstein-Barr virus may provoke immune cells to attack the brain, offering fresh hope for treating multiple sclerosis.

Scientists at UC San Francisco have identified a new piece of evidence that helps explain how Epstein-Barr virus (EBV) may contribute to multiple sclerosis (MS). MS is a long-lasting autoimmune disease that affects nearly one million people in the United States.

The research, published today (February 5) in Nature Immunology, points to a specific group of immune cells called CD8+ “killer” T cells. These cells normally eliminate infected or damaged cells. The study found that people with MS have higher levels of certain killer T cells, including cells that specifically react to EBV. This finding suggests the virus could be setting off the immune attack that damages the nervous system in MS.

Researchers have long suspected EBV plays a role in MS. The virus is extremely common, infecting about 95% of adults, and is found in almost everyone who later develops the disease.

“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 and member of the UCSF Weill Institute for Neurosciences.

Why Killer T Cells Matter

Multiple sclerosis develops when the immune system mistakenly attacks myelin, the protective coating around nerve fibers in the brain and spinal cord. Over time, this damage leads to worsening neurological problems.

Most MS research has traditionally focused on CD4+ T cells. These cells help coordinate immune responses but do not directly destroy cells. Scientists often study CD4+ T cells because they are easier to model in animals. CD8+ killer T cells, which can directly kill other cells, have been harder to examine in living patients.

To address this gap, Sabatino and his colleagues studied killer T cells directly in people.

Comparing Blood and Spinal Fluid

The research team analyzed blood and cerebrospinal fluid (CSF) samples from 13 people with MS or early signs of the disease, along with samples from five individuals without MS.

They focused on CD8+ T cells that recognized specific proteins present in these fluids. Among participants without MS, the number of these immune cells was similar in both blood and CSF.

In people with MS, however, the pattern was dramatically different. The protein-recognizing killer T cells were between 10 and 100 times more concentrated in the CSF than in the blood. This striking imbalance pointed to abnormal immune activity inside the central nervous system.

Epstein-Barr Virus Activity in the Nervous System

EBV itself was found in the CSF of most participants, regardless of whether they had MS. Some of the virus’s genes were also active. Notably, one EBV gene was active only in people with MS, suggesting it could be playing a role in driving the excessive immune response linked to the disease.

These results add to a growing body of evidence tying EBV to autoimmune conditions. Beyond MS, the virus has also been associated with lupus, rheumatoid arthritis, and long COVID.

Hope for New Treatments

Because of the strong connection between EBV and MS, some researchers are already testing treatments designed to target the virus.

“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.