In multiple sclerosis, overactive inflammatory immune cells destroy the tissue that surrounds and insulates the nerves. Now, new research in mice reveals that activating a different group of immune cells could potentially counteract the destructive autoimmune reaction.
Researchers at Stanford University School of Medicine in California suggest that their findings could lead to new treatments for autoimmune conditions, such as multiple sclerosis (MS) and celiac disease.
In a recent Nature paper, they describe how they studied immune cells in a mouse model of MS and also from people with the disease.
They found evidence to suggest that there is a balance between the type of immune cell that causes inflammation and another type of immune cell that can suppress it. It appears that the balance is upset in autoimmune disease.
Senior study author Mark M. Davis, a professor of microbiology and immunology at Stanford, suggests that it could be possible to restore the balance by selectively stimulating the protective immune cells.
"If we could mobilize those cells to function more effectively in patients with autoimmunity," he explains, "then we'd have a novel treatment for diseases like [MS]."
Millions living with autoimmune diseases
Autoimmune diseases are conditions in which the immune system attacks a part of the body as if its tissues and cells were a threat, such as invading bacteria and viruses.
There are at least 80 autoimmune diseases that scientists know about. These include MS, celiac disease, type 1 diabetes, rheumatoid arthritis, and lupus. Scientists do not know which molecules trigger the immune reactions behind most of these conditions.
In the United States, there are more than 24 million people with autoimmune diseases and another 8 million at risk of developing them. The number of people developing autoimmune diseases is rising, for reasons that are not clear.
Doctors find many autoimmune conditions challenging to diagnose, and people can wait for a long time for a definite diagnosis.
The majority of autoimmune diseases have no cure, and people have to take medicines for the rest of their lives to manage their symptoms.
Scientists see MS as an autoimmune disease in which inflammatory cells of the immune system attack the protective myelin sheath that surrounds the nerves fibers in the central nervous system (CNS).
Depending on which part of the CNS the disease strikes, the symptoms of MS can vary between individuals and also in the same person.
A recent population study suggests that over 900,000 people are living with MS in the U.S.
Activating suppressor cells
For their study, Prof. Davis and his colleagues studied immune cells in the blood of mice that they had induced to develop encephalomyelitis. This is a condition that inflames the brain and spinal cord in a similar way to MS.
They focused on a type of cell called CD8 T cells. They already knew that these cells could kill cancerous and infected cells. However, they also noticed an increase in these cells in the MS mouse model. They suspected that the cells were contributing to the disease.
The team was surprised to discover, however, that this was not the case.
When they injected the mice with peptides that the CD8 T cells could recognize, it led to the death of inflammation-causing T cells and a reduction in symptom severity.
To investigate this further, the researchers grew the two cell types in a dish. They found that activating the CD8 T cells with peptides stimulated them to pierce holes in the inflammatory T cells.
They suggest that — together with the discovery that the cells carry immune suppressing proteins on their surfaces — these findings confirm that CD8 T cells can be suppressor cells.
Could unbalanced cells cause autoimmunity?
The researchers compared blood from people with MS and those without it. They found that people with MS were more likely to have higher levels of cells that were clones of single CD8 T cells. This was the same in the mouse model.
When T cells spot a potential enemy agent, they identify a distinguishing molecular feature, or antigen, that helps them recognize the agent. They then replicate themselves to make large numbers of T cells that remember the specific antigen.
By running DNA tests on the increased CD8 T cells, Prof. Davis and his colleagues found that they were identical — the increased population comprised clones of single CD8 T cells.
Such a finding suggests that the CD8 T cells are homing in on a particular feature of the disease. The researchers hope to discover what it is and how it helps to spawn immune suppressing CD8 T cells.
The researchers suggest that the two types of cell — inflammatory T cells and activated immune-suppressing CD8 T cells — work in balance with each other and that autoimmune diseases could be due to them becoming unbalanced.
"We absolutely think that something like this is happening in human autoimmune diseases," Prof. Davis explains, adding that "it represents a mechanism that nobody's really appreciated."
The idea that some CD8 T cells have the power to suppress inflammation is not new. Scientists first proposed the notion in the 1970s, but interest dwindled as researchers focused predominantly on other features of immune cells.
The team is planning to extend the research to investigate the potential role of suppressive CD8 T cells in other autoimmune conditions.
"There's this whole subset of CD8 T cells that has a suppressive function."
Prof. Mark M. Davis