Study says potent cell plays big role in asthma

A little-known but potent cell in the immune system plays a far bigger role than had been previously thought in asthma, Children's Hospital Boston researchers have found, perhaps explaining why current treatments often fail to control the disease.

The new culprits, called natural killer T cells, were 100 times more abundant in the lungs of people who suffer frequent asthma attacks than in the lungs of healthy people, the researchers found.

They said they believe that these cells, which already have been shown to cause asthma in mice, play a leading role in the inflammation and the buildup of mucus in the airways of asthma patients.

Steroids, which are now the leading treatment for asthma, appear to have little effect on natural killer T cells, the researchers said, and no other treatment is known to work against them, either.

''When I first saw the results . . . I nearly fell off my chair," said Mark Exley, who is an immunologist at Beth Israel Deaconess Medical Center.

Exley, who was not part of the study, said, ''It's certainly a very different approach than anyone else has come up with to date."

The report, published in today's New England Journal of Medicine, points out the shortcomings in the pills and inhalers that most asthma sufferers use to manage the disease. Asthma afflicts 20 million Americans, triple the number in 1980.

Though steroids relieve asthma-related inflammation in the vast majority of patients, the drugs do not fully control symptoms in as many as 20 percent of patients, the researchers said.

People with asthma can develop diminished breathing capacity and routinely suffer attacks of wheezing and shortness of breath, prompting about 2 million emergency room visits each year in the United States. Roughly 5,000 people, including 200 children, die from these attacks.

Moreover, some people with asthma have to take such high doses of steroids to breathe normally that they increase their risk for debilitating side effects such as cataracts, glaucoma, or osteoporosis.

''If we can specifically eliminate natural killer T cells, we should be able to treat asthma much more effectively," said Dr. Dale Umetsu, a Children's Hospital Boston immunologist and coauthor of the study.

The root cause of asthma is unknown, but scientists generally know what happens when dust or strenuous exercise or some other irritant triggers an attack: The patient's immune system goes into overdrive in reaction to the irritant, causing inflammation and mucus buildup as immune-system cells mass in the lungs.

Until now, researchers have believed that a class of immune cells called type 2 helper cells were the leading cause of the inflammation, but the Children's Hospital researchers suspect that this may be a case of mistaken identity. The type 2 helper cells look a lot like natural killer T cells under a microscope, and the technique to clearly detect natural killers has existed only for a few years. As a result, Umetsu said, ''in the past what people thought were type 2 helper cells were really natural killer T cells."

The distinction is bigger than simply a difference in names. Natural killers are far rarer and stronger than type 2 helpers, the researchers said.

The natural killers are able to rapidly summon other cells in the immune system to help expel invaders. Umetsu and a research partner, Omid Akbari, discovered how potent natural killer T cells are in research at Stanford University in 2003: They caused symptoms of asthma in mice using only natural killer T cells.

Their research also found that in humans, natural killers, unlike type 2 helper cells, do not decrease in number when a patient takes steroids.

In the study, Umetsu, Akbari and their colleagues examined specimens from the lungs of 14 people with asthma, six healthy people, and five patients with a lung disease called sarcoidosis.

While the healthy people and the sarcoidosis patients had almost no natural killer T cells in their lungs, the people with asthma had enormous concentrations of natural killers.

In the asthma patients, more than 60 percent of the immune cells were natural killers.

''Conventional type 2 helper cells may not be as important in causing asthma as we thought," Umetsu said. ''We now believe that natural killer T cells may be equally or more important."

Even though the Children's researchers studied a small number of people, outside asthma specialists said their results were persuasive because the difference between the asthma patients' lungs and everyone else's was so large.

''It's a very exciting report," said Dr. George O'Connor, a pulmonologist and asthma researcher at the Boston University School of Medicine. ''These [natural killer T] cells may indeed be important in asthma. We have a lot to learn about what role they play . . . but it does open up a whole new avenue of research."

Umetsu said his lab is looking for a potential treatment that either expels natural killers from the lungs or cuts off the cells' ability to summon other cells. The lab has had limited success so far. However, he believes other asthma researchers will now join in the search for new treatments.

''Clearly, what we are proposing is a very new paradigm for asthma," he said.

Scott Allen can be reached at allen@globe.com.