A RECENTLY discovered class of
immune cell may hold the key
to new treatments for asthma –
and explain why existing
therapies sometimes fail.
Asthma occurs when immune
cells go into overdrive and release
inflammatory chemicals called
cytokines. These cause excess
production of mucus, which
plugs up the lungs. The disease
is generally associated with
immune cells called T-helper 2
(TH2) cells and the cytokines they
release, but their response alone
is not enough to trigger asthma.
Natural killer T (NKT) cells
produce some of the same
cytokines as TH2s, but release
them faster and in greater
quantities (see Diagram).
NKT cells are hybrids: they kill
invading microbes, like natural
killer immune cells, but they
also bind to antigens – foreign
substances that trigger an immune
response – like T-cells do.
Last year, Omid Akbari and
his colleagues at Children’s
Hospital Boston, Massachusetts,
discovered high numbers of NKT
cells in the lungs of people with
severe asthma, but virtually none
in the lungs of healthy people.
Meanwhile, separate studies in
mice have shown NKT cell
activation alone is enough to
trigger asthma, prompting
researchers to speculate that NKT
cells might be equally, or more,
important than TH2 cells in the
development of the disease.
Akbari’s team has now used a
drug called DPPE-PEG to inhibit
the action of NKT cells in mice and
found that it prevented the type of
asthma linked to allergies. DPPE-
PEG already has approval from the
US Food and Drug Administration,
so clinical trials could begin as
early as this year, says Akbari,
who presented his findings at a
meeting of the American
Academy of Asthma, Allergy and
Immunology in San Diego,
California, this week.
The findings may help explain
why some people with asthma are
resistant to conventional drugs
such as corticosteroids. These
inhibit many immune cells, but do
not work on NKT cells, Akbari says.
However, while DPPE-PEG
shows promise, more work is
needed to understand the role of
NKT cells in asthma. For a start,
they seem to bind to glycolipids –
molecules made from fats and
sugars – rather than the protein
antigens recognised by most
immune cells. Few glycolipid
antigens have been discovered so
far, although some have now been
identified in bacteria and pollen.
In the case of DPPE-PEG, Akbari
believes it works by blocking the
antigen receptors on NKT cells
and so preventing their immune
response. But since the allergen
his team used to trigger asthma
in the mice was an egg protein,
it is unlikely to have been this that
stimulated the NKT cells in the
first place. It could be that protein
allergens trigger the release of
naturally occurring glycolipids
by some as yet unidentified
mechanism, which then stimulate
NKT cells, suggests Akbari.
“It is also possible that there’s a
bacterial component to asthma,”
says Mitchell Kronenberg,
president of the La Jolla Institute
of Allergy and Immunology in
California. He suggests that
bacteria present in the body may
produce glycolipids that prime
NKT cells to respond when an
allergen is introduced. �
SOUNDBITES
‹ Talk with the patient while you are restraining him. Explain what you are doing and that you are using a restraint to ensure that he is safe.›
NASA instructions for restraining a
psychotic or suicidal fellow astronaut
using duct tape, bungee cords and
tranquillisers (AP, 24 February)
‹ We knew that we’d lost the war. Our psychological state was very strange by then. In those conditions, we could do anything, absolutely anything.›
Akira Makino, a former medical
auxiliary in the Japanese navy,
breaks a 60-year silence to describe
how he performed medical vivisection
on prisoners of war in the Philippines
(The Times, London, 26 February)
‹ This is one baby that clearly has come in from the cold.›
Michael Chapman of the Sydney clinic
IVF Australia, commenting on a baby
born last year after a woman’s frozen
egg and a donor’s frozen sperm created
an embryo that was then frozen.
Chapman believes the case is a first
(The Sydney Morning Herald, 27 February)
‹ The message to men is: ‘Wake up and smell the java – it’s not just about women any more, it’s about you too’.›
Pamela Madsen, executive director
of the American Fertility Association,
a national education and advocacy
group, alerts men to mounting
evidence that they too have a biological
clock (The New York Times, 27 February)
‹ The electronic signals resemble the signals generated by the brain that control body movement.›
Su Xuecheng of Shandong University
of Science and Technology, China, on a
pigeon with electrodes implanted in its
brain that allow him to control its flight
(Xinhua news agency, 27 February)
ARIA PEARSON
www.newscientist.com 3 March 2007 | NewScientist | 13
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NEW VERSION JUST RELEASED!
Asthma linked to hybrid immune cell
Bronchial tube in run-up
to an asthma atttack
NKT cells release cytokines in
response to allergens, triggering
inflammation. The air passages
become inflamed and mucus-filled
Inflamed bronchial tube
during an attack
ANOTHER ROUTE TO ASTHMA
NKT cell
Mucus
Cytokines
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