MS patients have high levels of T-cells targeting EBV-infected B-cells

People with multiple sclerosis (MS) have high levels of T-cells in their spinal fluid that specifically target cells infected with the Epstein-Barr virus (EBV), according to a new study.

These T-cells were found in samples collected from patients during their diagnostic workup in the early stages of disease. The findings may help to shed more light on the processes that drive MS.

“This work demonstrates that T-cells specific for [EBV-infected cells] are present in the cerebrospinal fluid at the earliest stages of disease,” J. William Lindsey, MD, professor at the McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), said in a press release.

This finding “strongly suggests that these T-cells are either causing the disease or contributing to it in some way,” Lindsey added.

The study, “Expanded T lymphocytes in the cerebrospinal fluid of multiple sclerosis patients are specific for Epstein-Barr-virus-infected B cells,” was published in PNAS.

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Epstein-Barr virus best known for causing ‘mono’

EBV is best known for causing infectious mononucleosis, colloquially called “mono,” though it more commonly causes nonspecific infections during childhood. The vast majority of people have been infected with EBV by the time they reach adulthood. After the infection, this virus resides dormant inside B-cells, a type of immune cell.

Although the causes of MS remain incompletely understood, infection with EBV has been identified as one of the strongest risk factors for developing MS. However, exactly how EBV may lead to MS is unclear, and most people infected with EBV don’t develop MS.

In MS, the body’s immune system mistakenly launches an attack targeting healthy parts of the brain and spinal cord. One theory for how EBV might lead to MS is that when the immune system attacks the virus, it may also accidentally start targeting healthy brain tissue.

If that’s the case, then it would be expected that people with MS would have high numbers of T-cells targeting EBV, as T-cells are a type of immune cell with a central role in defending against viral infections. In this study, researchers put this idea to the test.

“Our hypothesis is that a major fraction of the expanded clones of [T-cells] in the cerebrospinal fluid (CSF) are specific for … EBV-infected B cells,” the scientists wrote.

They collected T-cells from people with MS who were in the diagnostic process at the time. Then, they exposed the T-cells to cells infected with either EBV or other viruses, such as influenza and varicella zoster (the virus that causes chicken pox and shingles).

For these experiments, the scientists separately tested T-cells isolated from the patients’ blood, and also from the cerebrospinal fluid (CSF), which is the liquid around the brain and spinal cord.

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T-cells in CSF were most reactive to B-cells infected with Epstein-Barr virus

Results showed 13% of T-cells in the CSF of MS patients, as well as a similar percentage of cells from the patients’ blood, were specifically reactive to B-cells infected with EBV. By comparison, the next-most common target, influenza, was targeted by less than 5% of T-cells in CSF and less than 10% of T-cells in the blood.

The researchers then looked at the top 1% of most abundant T-cells in the CSF of the patients, and nearly half of them (47%) were specific to EBV.

“We saw a clear signal of enrichment of T-cells specific for [EBV-infected cells] in the cerebrospinal fluid from the multiple sclerosis patients. This pattern was very different from what we observed in other neurologic diseases, suggesting it is unique to multiple sclerosis,” said Assaf Gottlieb, PhD, a study co-author at UTHealth.

The researchers are now conducting more tests with the hope of better understanding the biological activity of these EBV-specific T-cells.

“We have experiments in progress to define what these cells may be doing,” Lindsey said.