Our body may produce its own special class of cells that block asthma and other allergic reactions, researchers from NYU Langone Medical Center conclude.
Every time we eat or inhale a potential allergen for the first time, a certain gene triggers the manufacture of custom-made immune cells, known as regulatory T cells (Treg), the new research reveals. These cells prevent an allergic response the next time the same substance is encountered.
“We often eat or breathe in allergens, but without having an allergic reaction,” says Maria A. Curotto de Lafaille, Ph.D., lead investigator and research assistant professor at NYU Langone Medical Center. “That’s because something very important is happening: we're making regulatory T cells. In turn, such cells recognize specific allergens and prevent us from developing allergies."
This finding provides a key to one of the most serious consequences of asthma. In addition to breathing problems during an acute attack, people with asthma have chronic inflammation, which can permanently damage their airways. If a means can be found to increase the number of Treg cells in inflamed tissue, this airway damage might be prevented.
The next step? "We're now investigating ways to grow allergen-specific Treg cells in the lab,” says Dr. de Lafaille. Then maybe someday “they can be injected into people who have some defects in their own Treg cells."
As this research demonstrates, when it comes to allergies, both the problem and the solution are found within us. Our immune systems respond to foreign substances with an arsenal of cells. Some are programmed to "remember" invaders they've encountered in the past. Normally, anything previously identified as harmless is allowed to pass. Sometimes, however, the immune response goes awry, triggering an allergic reaction.
Preventing Allergies vs. Suppressing Symptoms
This work represents an important step in understanding the genetic and cellular mechanisms underlying the allergic response, which may lead to more effective therapies. Current treatment is aimed at suppressing symptoms and reducing inflammation after an allergic reaction has occurred. Having identified the cell type that must be present to prevent allergies, Dr. de Lafaille and her colleagues are now looking for the glitch that blocks formation of those cells in allergic individuals.
As the study explains, mucosal tissue, which lines both the respiratory and digestive tracts, has long been known as an effective barrier against allergens, which are protein molecules. This research shows that Foxp3-containing regulatory T cells (Treg) are produced in the mucosal tissue and remain there to prevent allergic reactions. New ones are tailor-made every time an unknown protein is inhaled or ingested. The inability to make sufficient Treg cells results in high susceptibility to becoming allergic.
The researchers induced strong allergic reactions in mice with a Foxp3 gene mutation that prevented formation of Treg cells. Exposure to the same allergen—in this case egg protein—did not elicit an allergic response in mice that were able to make Treg cells.
The formation of Foxp3-positive Treg cells occurs in response to any potential allergen, so the findings are applicable to a broad range of allergic reactions and autoimmune diseases, says Dr. de Lafaille. When people suffer from allergies, including life-threatening ones such as asthma, something might have gone wrong in the process by which Foxp3-containing Treg cells are formed. The problem is not necessarily a mutation in the Foxp3 gene, which is known to cause severe autoimmune disease. Rather, something occurs, or fails to occur, in the lungs or the gut that interferes with the production or activity of allergen-specific Treg cells.
The researchers also determined that Treg cells control damage from long-term inflammation. They found high concentrations of Treg cells in inflamed lung tissue of mice without the Foxp3 defect.
More Important Than Inflammatory T cells
"The question arose about what these cells are doing in the tissue—are they beneficial or not?" Dr. de Lafaille says. It turns out that even though the Treg cells did not prevent inflammation in an ongoing allergic reaction, they kept it under control, ensuring it did not worsen or spread to other areas of the body. "We think that over time, as the exposure to allergens increases, these regulatory T cells become gradually more important than the inflammatory T cells, and end up shutting off the inflammation. But it's not overnight and it's not black and white," Dr. de Lafaille emphasizes.
"The big challenge is how to isolate the cells that will recognize the right allergens to which a person is allergic," Dr. de Lafaille says. Another approach is to stimulate the body to manufacture the cells itself, an area of ongoing research.
Illustration: Severe lymphoid infiltration and smooth muscle remodeling in tissue from mice with chronic inflammation in the absence of Treg cells. --New York University Langone Medical Center.
New York University Langone Medical Center News Release (07/21/08)
Science Daily (07/16/08)
Medical News Today (07/17/08)
Abstract (Immunity; Vol. 29, 114-126, 18 July 2008)