The human body has myriad defenses to protect itself from disease and infection, but sometimes those biological bulwarks can become a threat themselves when they attack healthy cells and tissues, often by mistake. This autoimmune mixup can create debilitating chronic conditions like multiple sclerosis (MS), which affects nearly two million people worldwide.
In MS, the immune system attacks a protective tissue called myelin, insulating the central nervous system. The resulting damage to nerves prevents the back-and-forth of messages across the body and underlies hallmark symptoms of the disease, like fatigue, numbness, tingling, and pain, among many others.
While there’s currently no cure for MS, developing a better understanding of what causes the disease can help lead to one. Scientists have hypothesized the autoimmune reaction is prompted by a mix of environmental and genetic factors, but that another important element could involve past infection with the Epstein-Barr virus (or EBV), which infects around 95 percent of adults worldwide and causes a condition also known as infectious mononucleosis. Now, researchers in Texas are piecing together how a previous EBV infection can catapult the development of MS.
In a study published Monday in the journal Proceeding of the National Academy of Sciences, a team of researchers from the University of Texas Health Science Center at Houston found that a critical immune cell called a T cell was in high numbers in the cerebrospinal fluid of eight people in the early stages of MS.
“This strongly suggests that these T-cells are either causing the disease or contributing to it in some way,” co-author J. William Lindsey, a professor of neurology at UTHealth Houston, said in a press release. “We have experiments in progress to define what these cells may be doing.”
T cells are a type of white blood cells that help identify and destroy infected cells. They also orchestrate a wider immune response to health threats by signaling to other immune cells, like antibody-producing B cells, and non-immune cells.
In the new study, Lindsey and his colleagues drew blood and cerebrospinal fluid samples from patients who were being diagnosed with MS. They exposed the cells in the blood samples to B cells transformed after an EBV infection (called an EBV-infected lymphoblastoid cell line); other viruses like varicella zoster (which causes chickenpox) and influenza; and the fungus candida.
After a few days, the researchers sorted out the cells that responded to these infections and focused on analyzing the T cell receptors, which are like unique identifiers showing what each T cell is targeting. By comparing the T cell receptors from the blood and cerebrospinal fluid, the researchers could figure out which infections elicited a response from T cells.
On average, most of the T cells in the cerebrospinal fluid — around 13 percent of them — were sensitive to the EBV-infected lymphoblastoid cells (this was equivalent to T cells in the blood samples). They weren’t as comparably sensitive to varicella, influenza, or candida. This suggested to Lindsey and his colleagues that there was some clear link between T cell activity triggered by EBV and MS.
“This pattern was very different from what we observed in other neurologic diseases, suggesting it is unique to multiple sclerosis,” first author Assaf Gottlieb, an assistant professor at UTHealth Houston’s School of Biomedical Informatics, said in the press release.
This finding still doesn’t explain how the T cells are contributing to the development of the disease, but it’s a first step in that direction. Previous studies have found that antibodies produced in response to EBV may mistakenly go after the brain and spinal cord. T cells may also be doing the same, misfiring and mistakenly attacking healthy nerve tissues.
However, since only a small percentage of people infected with EBV actually go on to develop MS, the virus alone isn’t enough to trigger the disease. Further research will require tying in the immune system with other unknown factors — whether genetic or environmental — and as studies in mice suggest, deeper insights may hopefully solidify the possibility of reducing the risk of MS with vaccines against EBV.
Although a cure for MS might still be on a far distant horizon, these new discoveries are steadily charting the course toward eventually conquering this complex disease.
