The immune system's CD8 T cells are best known for their ability to root out cancer. But researchers at Stanford University School of Medicine may have found another role for these T cells: They can also kill wayward immune cells that cause multiple sclerosis.
When the researchers injected peptide proteins into mice to boost their levels of CD8 T cells, the severity of their MS symptoms dropped, they reported in the journal Nature. When they performed a similar test in cells taken from patients with MS, they observed the same phenomenon.
“There's this whole subset of CD8 T cells that has a suppressive function," said senior author Mark Davis, Ph.D., professor of microbiology and immunology at Stanford, in a statement. “If we could mobilize those cells to function more effectively in patients with autoimmunity, then we'd have a novel treatment for diseases like multiple sclerosis."
The Stanford team started with a mouse model of MS that was made by injecting the animals with the peptide myelin oligodendrocyte glycoprotein (MOG). They tracked all of the immune cells in the mice after injection and discovered that while some types of T cells did grow, some CD8 T cells didn’t respond at all to the peptide.
So they decided to generate 5 billion other peptides in the lab, attach them to yeast cells, then expose different T cells to them to see what caused a response. They found two peptides that when administered along with MOG could reduce or prevent MS symptoms in mice.
Further studies revealed that when CD8 T cells were exposed to the two peptides, they responded by hunting down autoimmune-disease-causing T cells and killing them by breaking their cell membranes. Large populations of identical CD8 T cells were also found in the cell samples they studied from people with MS.
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Much of the current research in MS is focused on rebuilding myelin, the protective sheath around neurons that breaks down in the disease and other neurodegenerative disorders. Scientists at the VA Maryland Health Care System and the University of Maryland School of Medicine said earlier this year that they’ve seen promising preclinical results from melanocyte-producing stem cells, for example. A University of Chicago team is focused on repurposing an old blood pressure drug, Wytensin, in MS due to its myelin-protecting properties.
The Stanford researchers were surprised to discover that activating CD8 T cells with peptides could protect against MS, even though the notion that the cells may have immunosuppressive powers was first proposed in the 1970s. The idea of pursuing therapies that target CD8 T cells died when early studies produced disappointing data.
The next step for the Stanford team is to try to determine what CD8 T cells are recognizing in MS that causes them to respond in a therapeutic way. The researchers are also interested in studying the role of CD8 T cells in other disorders, including celiac disease.