Killer immune cells targeting Epstein-Barr virus may help drive MS
Study provides 'new window' on link between EBV and MS
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A 3D rendered image shows a virus.
- MS may be driven by Epstein-Barr virus reactivation in the brain.
- MS patients show high levels of EBV-fighting CD8 T-cells in spinal fluid.
- Targeting EBV could offer a new treatment strategy for MS.
A type of immune cell that has received little attention in multiple sclerosis (MS) research may play a key role in driving the disease.
A study found that some people with MS had abnormally high levels of virus-fighting CD8 T-cells in the fluid surrounding the brain and spinal cord. Many of these cells were primed to recognize the Epstein-Barr virus (EBV), offering new insight into how the virus may be involved in 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,” Joe Sabatino, MD, PhD, senior author of the study and an assistant neurology professor at the University of California San Francisco, said in a university news story.
The study, “Antigen specificity of clonally enriched CD8+ T cells in multiple sclerosis,” was published in Nature Immunology. The work was funded by the National Institutes of Health, the Japan Society for the Promotion of Science, and the National Multiple Sclerosis Society, among others.
Most people harbor Epstein-Barr virus; why do some develop MS?
MS is a chronic disorder in which the immune system mistakenly attacks healthy tissue in the brain and spinal cord. While the exact causes of MS are not fully understood, infection with EBV has emerged as a major risk factor.
The vast majority of people are infected with EBV at some point in their lives. In most cases, the virus doesn’t cause serious illness and remains dormant in the body after the initial infection. But some people infected with EBV go on to develop MS, for reasons that are poorly understood.
T-cells are a type of immune cell that help the body fight infections. Each T-cell is equipped with a molecular receptor — called a T-cell receptor (TCR) — that identifies a specific target, usually a piece of a virus.
When the receptor binds its target, the T-cell becomes activated and replicates to make identical cells carrying the same TCR, which can then help fight the threat. If many T cells carry a particular receptor, it implies that the immune system is actively responding to a threat.
An international team of scientists conducted detailed analyses of the TCR profiles in T-cells isolated from the blood and the cerebrospinal fluid (CSF), or the fluid around the brain and spinal cord. The study involved 13 people with relapsing-remitting MS or clinically isolated syndrome, an early disease stage defined as a first episode of MS-like symptoms, as well as five people who did not have MS.
The researchers specifically looked for TCRs that were more common in CSF than in blood, suggesting that these T-cells are engaged in an immune response in the brain and spinal cord.
The researchers identified more than two dozen such enriched T-cell clones. These cells were found in people with and without MS, but the specific receptors they carried differed, suggesting that what these cells target — not simply their presence — may be important in driving the disease.
There are multiple types of T-cells. Most MS research has focused on CD4 T-cells, which act as the field commanders of the immune system. When their TCR binds its target, these cells produce molecules signaling other immune cells to go on the offensive.
In the study, however, most of the T-cell clones expanded in the CSF were CD8 T-cells, a less-studied subtype that directly kills infected or abnormal cells.
In several MS patients, these expanded CD8 T-cells carried receptors that specifically recognized EBV. Additional analyses showed increased activity of certain EBV genes in these patients, suggesting the virus may be active in the brain and spinal cord.
Taken together, the findings suggest that EBV may become reactivated in the brains of some people with MS, prompting CD8 T-cells to attack infected cells and potentially triggering inflammation.
If confirmed, this mechanism could help explain how EBV contributes to MS and support efforts to develop treatments that target the virus. Several experimental therapies targeting EBV are already being tested for MS.
“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.
