“Abnormal” T killers, white blood cells that become a threat to the body. Found the person responsible for the transformation from good to bad: the STAT3 protein
This new research provides insight into the role of killer T cells (the T lymphocyte, of the white blood cell family, whose function is to eliminate viruses, bacteria and other pathogens in the body) in leukemia and autoimmune diseases. Scientists had previously noted that patients with leukemia were also likely to develop an autoimmune disease (which occurs when the immune system attacks cells in the body, mistaking them for harmful or foreign cells). Research into this link has revealed that immune cells, killer T lymphocytes , play a key role.
Gene variants associated with leukemia can produce ‘abnormal’ killer T immune cells that cause autoimmune diseases, according to a new study from the Garvan Institute of Medical Research.
Researchers have found that changes affecting the STAT3 protein , which controls the growth of killer T lymphocytes during conditions such as leukemia and other autoimmune diseases (eg, rheumatoid arthritis, multiple sclerosis, Hsshimoto’s disease, lupus) can transform T lymphocytes into abnormal and dangerous cells.
“Our research also narrows down some pathways that could be useful for targeting these cells for future treatments ,” says Etienne Masle-Farquhar, of Garvan’s immunogenics and genomic medicine labs.
“We knew that people with various autoimmune diseases acquire these abnormal killer T cells over time, but also that inflammation can cause immune cells to proliferate and develop mutations. We wanted to find out whether the abnormal T cells were the cause of these autoimmune conditions or simply associated with them,” Masle-Farquhar explains. To do so, the researchers used new high-resolution screening methods to examine the blood of children with rare inherited autoimmune diseases.
The team found that if these proteins are altered, they can cause killer T cells to grow uncontrollably, resulting in their enlargement. Also, a significant fact that has emerged is that as little as 1-2% of a person’s T lymphocytes could cause an autoimmune disease.
“It has never been clear what the link between leukemia and autoimmune disease is: whether the altered STAT3 protein underlies the disease or if leukemia cells divide and acquire this mutation as a by-product, Masle-Farquhar’s work was able to solve this conundrum,” says Professor Chris Goodnow, head of the Immunogenomics Laboratory. “This allows us to understand where we could do better to stop these diseases, which are sometimes life-threatening,” concludes the professor.
The team’s research could help develop screening technologies that doctors could use to sequence the complete genome of every cell in a blood sample, to identify which cells might be dangerous and cause disease. More studies are needed to determine whether abnormal killer T cells are involved in all autoimmune diseases and what percentage of people with rheumatoid arthritis and other autoimmune diseases have abnormal cells and STAT3 protein changes.
- STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological NKG2Dhi CD8+ T cell dysregulation and accumulation. (cell.com)