Forgotten immune cells protective in mouse model of MS

August 09, 2019
A seldom-studied class of immune cells may reduce the friendly fire that drives autoimmune disease, according to a new study. Stimulating these protective cells could lead to new therapies for multiple sclerosis. 

In the study, researchers at the Stanford University School of Medicine tracked immune cells in the blood of mice with a disease akin to MS. They discovered a rise in CD8 T cells, typically known for killing infected or cancerous cells. To their surprise, injecting mice with peptides recognized by these CD8 T cells reduced disease severity and killed disease-causing immune cells. 

While the bulk of the study was done in mice, the researchers also showed that one of their central findings — an increase in CD8 T cells derived from single cells — held true in cells from people with MS. The findings suggest that inflammatory and suppressive immune cells balance each other like children on a seesaw. Selectively activating suppressive CD8 T cells during autoimmune disease may help restore that balance. 

In most cases, researchers don’t know what molecules trigger autoimmune diseases. MS is no exception. But scientists can trigger a similar disease in mice by injecting them with a small chunk, or peptide, of a protein called myelin oligodendrocyte glycoprotein, or MOG. Mice with the disease, known as experimental autoimmune encephalomyelitis, develop paralysis just like patients with MS. The researchers used this mouse model of the disease to investigate what different immune cells were doing during autoimmunity. They tracked the abundance of various classes of immune cells in mice injected with MOG.

They found that the number of T cells rose and fell like waves. DNA sequencing showed that those waves were each made of groups of identical cells — an important clue. 

The researchers tested roughly 5 billion peptides. The researchers found two peptides recognized by CD8 T cells involved in the disease. To understand the role of these peptides, they injected them into mice before, after, or alongside MOG. Since CD8 T cells are mainly known for killing cancerous and infected cells, the scientists expected that activating these cells would worsen disease. They were wrong. Activating the CD8 T cells by administering the two peptides consistently reduced or prevented disease in the mice. It was the exact opposite of what they’d expected.

The researchers found that these peptide-activated CD8 T cells killed disease-causing T cells by punching holes in their cell membrane when grown together in a dish. The CD8 T cells were also coated with surface proteins associated with immunosuppression — yet another clue that these cells were in fact suppressor CD8 T cells. 

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, to determine whether their mouse observations held up in humans, the researchers isolated CD8 T cells from the blood of people with MS and healthy donors. They found that people with the disease tended to have large populations of identical CD8 T cells — just like in mice with the analogous disease. It’s a sign that CD8 T cells in MS are homing in on something.

The study was published in the journal Nature.

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