Study Says Absence of Specialized Cells Linked to Asthma

Absence of specialized cells that block allergic reactions may increase the risk of developing asthma and allergies, according to researchers from NYU School of Medicine.

The researchers have identified a class of custom-made T-cells manufactured according to instructions from a gene called Foxp3 whenever we eat or inhale a potential allergen for the first time.

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"We don't become allergic to lots of things-we eat all kinds of things, we breathe all kinds of things, and what prevents us from developing allergies is that we make regulatory T cells, which specifically recognize this allergen," said Maria A. Curotto de Lafaille, Ph.D., Associate Research Scientist at NYU Langone Medical Centre.

"Every time we don't react to something or don't become allergic, it's not because nothing is happening. It's because something very important is happening: We're making these cells," de Lafaille added

Mucosal tissue, which lines both the respiratory and digestive tracts, has long been known as an effective barrier against allergens, which are always protein molecules.

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An allergy is a hypersensitive disorder of immune system. Substances that often cause allergic reactions are pollen, dust mites, mold spores, pet dander, food, insect stings and medicines.

The new study shows that Foxp3-directed 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.

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The inability to make Treg cells results in high susceptibility to becoming allergic.

For the study, the researchers induced allergic reactions in mice with a Foxp3 mutation that prevented formation of Treg cells and found that 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.

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It also showed 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.

"The question arose about what these cells are doing in the tissue-are they beneficial or not?" said Dr. de Lafaille. 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.

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 could be found to increase the number of Treg cells in inflamed tissue, this might be prevented.

The findings are reported in the July 18, 2008, issue of the journal Immunity.

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