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A new asthma target?

Current thinking about asthma attributes its inflammatory process to CD4+ T lymphocytes, specifically those known as type 2 helper (Th2) cells. Inhaled corticosteroids, a mainstay of asthma therapy, are thought to limit the function of these Th2 cells and thereby reduce asthma inflammation. But researchers in Children's Hospital Boston's Division of Immunology and Allergy now suggest that an entirely different cell type may be causing asthma, perhaps explaining why current Th2-focused therapies sometimes fail.

In 2003, Children's immunologist Dale Umetsu, MD, PhD, then at Stanford University, showed that natural-killer T cells (NKT cells) were required for the development of asthma in mice. This year, in the February 21 edition of the Proceedings of the National Academy of Sciences, Dr. Umetsu and Stanford graduate student Everett Meyer went on to show that activation of NKT cells was sufficient to cause asthma in mice, even in the absence of Th2 cells. "This was unexpected," Dr. Umetsu says. "But to apply these findings to humans, we had to examine patients with asthma."

In the March 16 New England Journal of Medicine, Dr. Umetsu and Children's collaborator Omid Akbari, PhD, did just that, and showed that NKT cells are abundant in the lungs of asthma patients. Specimens from the lungs of 14 adults with moderate-to-severe bronchial asthma revealed that the majority of their pulmonary T cells were actually 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 pulmonary levels of CD4+ T cells). These observations strongly suggest that NKT cells play a vital role in human asthma.

"NKT cells have many features of Th2 cells and can look like Th2 cells, but they don't respond to steroids," Dr. Umetsu says. "If we can specifically eliminate NKT cells, we should be able to treat asthma much more effectively."

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