If you sneeze your way through ragweed season or need a restraining order against your neighbor’s cat, researchers finally know what part of your immune system you should blame. A new study nails down the specific group of cells that orchestrates allergic reactions, a result that could help scientists determine not only why some people have allergies, but also how to block them.
“It’s exciting for those of us who are looking at potential ways to treat allergic diseases,” says Thomas Casale, an allergist and immunologist at the University of South Florida in Tampa who wasn’t connected to the study.
Allergies stem from mistaken identity, when some of our immune cells respond to benign substances—known as allergens—that include pollen, mold spores, and certain foods. Researchers know that the culprits that touch off allergic symptoms belong to a group of T cells known as TH2 cells. But not all TH2 cells are culpable. Some guard us against parasites and other invaders. Sorting the beneficial TH2 cells from the rogues has proved difficult, however.
In the new study, researchers led by T cell biologist Erik Wambre and immunologist William Kwok of the Benaroya Research Institute at Virginia Mason in Seattle, Washington, obtained blood samples from patients who were sensitive to pollen from alder trees, a common cause of winter and spring allergies. An allergic patient’s TH2 cells recognize and respond to an allergen because they carry receptors, proteins that match allergen molecules. To tag immune cells carrying receptors for alder pollen, the team added customized fluorescent proteins known as MHCII tetramers to the patients’ blood samples.
Along with receptors, TH2 cells are dotted with marker proteins. Like sports fans wearing their favorite team’s jersey, immune cells proclaim their identity with these marker proteins. The researchers analyzed the tagged cells to determine their combination of markers. Compared with other TH2 cells, one group sported more copies of two marker proteins and fewer copies of four others. Although none of the proteins was exclusive to the cells, together they provided a signature for this clique of TH2 cells, which the researchers dubbed TH2A cells. T cells can sometimes shift identifies, but the researchers found that TH2A cells remained distinct, even after several cellular generations. “When these cells are born, they are born to be pathogenic,” Wambre says.
As they report online today in Science Translational Medicine, Wambre, Kwok, and colleagues found that the cells were abundant in the blood of patients with allergies to a variety of triggers, including grass pollen and house dust mites. But they were absent from the blood of people who weren’t sensitive. The team also tested patients undergoing an experimental treatment called oral immunotherapy to alleviate their peanut allergies. Over about 20 weeks, the participants receive larger and larger doses of allergy-inducing peanut proteins, and this repeated exposure eventually allows them to tolerate peanuts.
“We saw a dramatic decrease in TH2A cells after the success of the treatment,” Wambre says. The number of these cells in the patients that reacted to peanuts fell by about 90%. Kwok says that the evidence he and his colleagues have accumulated suggests that “people with allergies make this specific subset of T cells that probably lead to allergic symptoms.”
The work could ultimately benefit patients through new treatments and better ways to monitor the disease, says immunologist Andrew Luster of Massachusetts General Hospital in Charlestown. For example, he notes, scientists could assess trials of oral immunotherapy—which attempts to quell patients’ allergies with edible doses of food allergens—by tracking which treatments were eliminating TH2A cells. Another option, Kwok adds, is that if researchers can determine what molecular signals steer certain T cells to become TH2A cells, they may be able to develop ways to prevent formation of the cells. If researchers succeed in that, they might also prevent a lot of sniffling and scratching.