Its all over the news,was an NPR report yesterday about it:
Source:

http://www.sciencedaily.com/releases/2006/03/060317120554.htm

Article:"New View Of Asthma's Cause: Previously Unrecognized Immune
Cell May Provide A Better Target For Therapy

A newly recognized type of immune cell may play an important role in
causing asthma, perhaps explaining why current therapies sometimes
fail, report researchers from Children's Hospital Boston in the March
16th New England Journal of Medicine. These immune cells, known as
natural-killer T cells (NKT cells), were found to be abundant in the
lungs of patients with asthma, but virtually absent in the lungs of
healthy people, supporting recent findings in mice showing a direct
causative role for NKT cells.

"Our findings were unexpected," says Dale Umetsu, MD, PhD, an
immunologist at Children's Hospital Boston and senior investigator on
both the human and mouse studies. "They suggest we need to look at
asthma in a different way in terms of therapies."

Asthma affects 20 million people in the U.S., and in 2003 caused nearly
2 million emergency-department visits. Previously, scientists believed
that conventional CD4+ T lymphocytes -- specifically, type 2 helper
cells (Th2 cells) -- were causing the inflammatory process that is
central in the disease. Corticosteroids, the current mainstay of asthma
therapy, target Th2 cells, along with other inflammatory cells.

But in 2003, Umetsu and co-investigator Omid Akbari, PhD, both then at
Stanford University, showed in Nature Medicine that activation of NKT
cells is required for the development of asthma in mice: Mice that
lacked NKT cells did not develop airway hyperreactivity, a cardinal
feature of asthma. And this year, in the February 21 Proceedings of the
National Academy of Sciences (PNAS), Umetsu and Stanford graduate
student Everett Meyer went on to show that NKT-cell activation alone is
sufficient to cause asthma in mice, even when Th2 cells are completely
absent.

"These findings were intriguing," Umetsu says. "But to apply them to
humans, we needed to examine patients with asthma."

In the New England Journal of Medicine study, Umetsu and Akbari, both
now in Children's Hospital Boston's Division of Immunology, did just
that. They examined specimens from the lungs of 25 adults: 14 with
moderate-to-severe bronchial asthma, 6 healthy subjects and 5 patients
with sarcoidosis, a respiratory inflammatory disease. They demonstrated
that, on average, at least two-thirds of the asthma patients' pulmonary
T cells were actually NKT cells, not conventional Th2 cells. In
contrast, NKT cells were virtually absent in the lungs of healthy
subjects and in patients with sarcoidosis (chosen as a control group
because their lungs have high levels of CD4+ T lymphocytes).

"Conventional Th2 cells may not be as important in causing asthma as
was thought," says Umetsu, also a Professor of Pediatrics at Harvard
Medical School. "We now believe that NKT cells may be equally or more
important. They produce the same cytokines [chemical messengers that
affect the immune response] as Th2 cells, and therefore theoretically
could completely replace Th2 cells in the development of asthma."

Umetsu and Akbari believe that NKT cells may have been mistaken for
conventional Th2 cells in the past because they carry many of the same
molecular markers. Since NKT cells constitute only 0.1 percent of
circulating white blood cells, they were easy to miss; only recently
have researchers had the techniques to be able to isolate and study
them.

A rapid, direct effect

Th2 cells are part of the adaptive immune system, which requires
exposure to antigens before a response can be mounted. They are thought
to work through other cells (such as eosinophils and B cells) to cause
asthma. In contrast, NKT cells are part of the innate immune system,
which is inborn and ready to respond rapidly to external threats. In
the February PNAS study, activation of NKT cells induced asthma
independently of eosinophils and B cells.

"NKT cells are the 'BMWs' of the immune system," says Akbari. "They can
produce cytokines very rapidly and directly cause asthma."

NKT cells have another unique property: while conventional T cells
recognize protein antigens, NKT cells are triggered by glycolipid
antigens.

"In the past, most of the focus in allergy and asthma has been on
protein antigens," Umetsu says. "Our current studies suggest that other
classes of antigens may be involved. And since NKT cells have a
receptor that varies little between mice and humans, we believe that
the antigens they recognize are very important. These findings open
whole new areas of research."

The still-unidentified glycolipid antigens that NKT cells "see" in
asthma may come from plant pollens, bacteria, or even the body itself.
Understanding their origins and how they activate NKT cells to cause
asthma may reveal new biological pathways that can be targeted by
drugs, the researchers say.

In addition to searching for these antigens, Umetsu, Akbari and
colleagues plan to look at milder asthma and extend their studies to
children to see if NKT cells play a similar role. They will also seek
ways of switching off or counteracting NKT cells, which could be
developed into new drugs.

Corticosteroids, which target Th2 cells and other inflammatory cells,
reduce inflammation but appear to have little effect on NKT cells,
Umetsu says. This perhaps explains why they don't always work in
asthma.

"If we can specifically eliminate NKT cells, we should be able to treat
asthma much more effectively," Umetsu says.
###

Umetsu's other collaborators include Rosemarie DeKruyff, PhD, in
Children's Division of Immunology, and John Faul, MD, currently at
Connolly Memorial Hospital, Dublin, Ireland. The research was funded by
the National Heart Lung Blood Institute, the National Institute of
Allergy and Infectious Diseases and the American Lung Association of
California. "