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Science Forum Index » Immunology Forum » Regulatory T-cell numbers directly related to allergic...
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| Kofi... |
 Posted: Sun Jul 20, 2008 1:45 am |
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This shouldn't come as a shock given that helminths raise regulatory
T-cell numbers and areas with high helminth infection rates have almost
no allergies.
http://www.sciencedaily.com/releases/2008/07/080714155301.htm
Researchers Identify Immune Cells That Block Allergic Reactions
ScienceDaily (July 16, 2008) ‹ When it comes to allergies, both the
problem and the solution are found within us. Our immune systems respond
to foreign substances with an arsenal of cells. Some are programmed to
"remember" invaders they've encountered in the past. Normally, anything
previously identified as harmless is allowed to pass. Sometimes,
however, the immune response goes awry, triggering an allergic reaction.
Now, researchers at NYU Langone Medical Center have zeroed in on a class
of custom-made immune cells that block allergic reactions. These
regulatory T cells are manufactured according to instructions from a
gene called Foxp3 whenever we eat or inhale a potential allergen for the
first time, ensuring that the next time we encounter that substance, we
will not mount an allergic response.
"We don't become allergic to lots of things--we eat all kinds of things,
we breathe all kinds of things, and what prevents us from developing
allergies is that we make regulatory T cells, which specifically
recognize this allergen," says Maria A. Curotto de Lafaille, Ph.D.,
research assistant professor of pathology at NYU Langone Medical Center.
"Every time we don't react to something or don't become allergic, it's
not because nothing is happening," Dr. de Lafaille explains. "It's
because something very important is happening: We're making these cells."
Mucosal tissue, which lines both the respiratory and digestive tracts,
has long been known as an effective barrier against allergens, which are
always protein molecules. The NYU research shows that Foxp3-directed
regulatory T cells (Treg) are produced in the mucosal tissue and remain
there to prevent allergic reactions. New ones are tailor-made every time
an unknown protein is inhaled or ingested. The inability to make Treg
cells results in high susceptibility to becoming allergic.
The NYU researchers induced allergic reactions in mice with a Foxp3
mutation that prevented formation of Treg cells. Exposure to the same
allergen--in this case egg protein--did not elicit an allergic response
in mice that were able to make Treg cells.
The formation of Foxp3-positive Treg cells occurs in response to any
potential allergen, so the findings are applicable to a broad range of
allergic reactions and autoimmune diseases, says Dr. de Lafaille. When
people suffer from allergies, including life-threatening ones such as
asthma, something goes wrong in the process by which Foxp3 signals Treg
cell formation. The problem is not necessarily a mutation in the Foxp3
gene, which is known to cause severe autoimmune disease. Rather,
something occurs, or fails to occur, in the lungs or the gut that
interferes with the production of allergen-specific Treg cells.
The NYU researchers also determined that Treg cells control damage from
long-term inflammation. They found high concentrations of Treg cells in
inflamed lung tissue of mice without the Foxp3 defect. "The question
arose about what these cells are doing in the tissue--are they
beneficial or not?" Dr. de Lafaille says. It turns out that even though
the Treg cells did not prevent inflammation in an ongoing allergic
reaction, they kept it under control, ensuring it did not worsen or
spread to other areas of the body. "We think that over time these
regulatory T cells become more important than the inflammatory cells and
end up completely shutting off the inflammation. But it's not overnight
and it's not black and white," Dr. de Lafaille emphasizes.
This finding provides a key to one of the most serious consequences of
asthma. In addition to breathing problems during an acute attack, people
with asthma have chronic inflammation, which can permanently damage
their lungs. If a means could be found to increase the number of Treg
cells in inflamed tissue, this might be prevented. Allergic asthma, the
most common and best-understood type, affects more than 10 million
people in the US, many of them children. Acute asthma attacks are
responsible for nearly 4000 deaths in the United States each year.
Dr. de Lafaille and her colleagues have been investigating ways to grow
allergen-specific Treg cells in the lab and inject them into people who
cannot make their own. Her group published a paper in Nature Medicine in
February 2008 describing a method of making the cells. "The big
challenge is how to isolate the cells that will recognize the right
allergens that the person is allergic to," she says. Another approach is
to stimulate the body to manufacture the cells itself, an area of
ongoing research.
This work represents an important step in understanding the genetic and
cellular mechanisms underlying the allergic response, which may lead to
more effective therapies. Current treatment is aimed at suppressing
symptoms and reducing inflammation after an allergic reaction has
already occurred. Having identified the cell type that must be present
to prevent allergies, Dr. de Lafaille and her colleagues are now looking
for the glitch that blocks formation of those cells.
The findings are reported in the July 18, 2008, issue of the journal
Immunity. The co-authors of the study include: Dr. de Lafaille, Nino
Kutchukhidze and Shiqian Shen, former postdoctoral students in
pathology, Yi Ding, a graduate student in pathology, and Herman Yee,
M.D., Ph.D., associate professor of pathology, and Juan J. Lafaille,
Ph.D., associate professor of pathology and Medicine at NYU Langone
Medical Center.
The research was supported by grants from the National Institutes of
Health, the National Multiple Sclerosis Society, and the Sandler
Foundation.
------------------------------------------------------------------------
Adapted from materials provided by NYU Langone Medical Center / New York
University School of Medicine, via EurekAlert!, a service of AAAS.
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