A newly recognized type of cell may play an important role in asthma, perhaps explaining why current therapies sometimes fail, report Dale Umetsu, MD, PhD, and Omid Akbari, PhD, in Children's Hospital Boston's Division of Immunology. A study in asthma patients, published in the March 16 New England Journal of Medicine, provides the latest evidence that immune cells, known as natural-killer T (NKT) cells, are key in asthma's development.
Previously, conventional CD4+ T lymphocytes - specifically, type 2 helper (Th2) cells - were believed to cause the inflammatory process that is central to asthma. Th2 cells are the target of corticosteroids, the mainstay of asthma therapy, but these drugs don't always work.
In 2003, while at Stanford University, Umetsu and Akbari showed that in mice, asthma development requires the activation of NKT cells: animals without NKT cells did not develop airway hyperreactivity, a cardinal feature of asthma. In February 2006, Umetsu and Stanford graduate student Everett Meyer further showed that NKT-cell activation can cause asthma in mice even when Th2 cells are completely absent.
Intrigued, Umetsu and Akbari decided to study human patients. They examined lung specimens from 14 adults with moderate-to-severe bronchial asthma, and found that, on average, at least two-thirds of the patients' pulmonary T cells were NKT cells, not conventional Th2 cells. In contrast, NKT cells were virtually absent in six healthy controls and in five patients with sarcoidosis (a respiratory inflammatory disease marked by high lung levels of CD4+ T cells).
"Conventional Th2 cells may not be as important in causing asthma as was thought," Umetsu says. "If we can specifically eliminate NKT cells, we should be able to treat asthma more effectively."
Interestingly, NKT cells produce the same chemical messengers as Th2 cells, but induce asthma more rapidly and directly. They also seem to be triggered by a unique class of antigens known as glycolipids, whose origins are still unknown."Most of the focus in asthma has been on protein antigens," Umetsu says. "This finding opens a whole new area of research."
Rosemarie DeKruyff, PhD, also from Immunology, collaborated on the study.
