Scientists have now identified a new type of human T cell that quells assaults on healthy tissues, a finding that could suggest treatments for conditions as diverse as lupus and cancer.
The price for a vigilant immune system that can pounce on tumor cells or pathogens is occasional friendly fire—an autoimmune attack. “It’s a major step forward in understanding how the immune response and autoimmunity are regulated,” says immunologist Harvey Cantor of the Dana-Farber Cancer Institute, who wasn’t involved in the work.
One obstacle was that humans don’t make the distinctive receptors that mark the subset of CD8 cells in mice. However, some human CD8 T cells flaunt comparable receptors, the KIR proteins. To determine whether these human cells are immune inhibitors, Jing Li, a postdoc in the lab of immunologist Mark Davis at Stanford University’s School of Medicine, and colleagues measured their abundance in patients with autoimmune diseases such as multiple sclerosis, lupus, and celiac disease. The.
To investigate the cells’ role in autoimmunity, the scientists homed in on celiac disease, which is triggered by the gluten proteins in bread and other grain-based foods. In patients with the condition, so called helper T cells recognize gluten proteins such as gliadin and then spill molecules that promote inflammation. But in cell culture studies, Li and colleagues found, human CD8 T cells carrying KIR proteins killed the gliadin-detecting helper T cells.
Cantor and other scientists are convinced the team has fingered the long-sought human counterparts to the rodent immune regulators. “The paper provides really solid data that these cells exist in humans,” says immunologist Nu Zhang of the University of Texas Health Science Center, San Antonio. They may have remained obscure because they “are rare and are easily missed,” accounting for only about 5% of CD8-positive T cells, Davis says.
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