News and Research
Immune System
Immune Response Depends On Key Molecule, According To
New Study
4-1-2003
In a new study published in the April 1, 2003 issue of Genes
and Development, scientists at University Health Network's
Advanced Medical Discovery Institute (AMDI)/Ontario Cancer
Institute (OCI) have shown that a molecule called caspase-8
plays a key role in the immune system response, by controlling
how T-cells are activated to respond to infections.
T-cells
are white blood cells that recognize and fight off viruses
and bacteria. When T-cells encounter these foreign invaders
they build up a T-cell "army" by multiplying themselves
many thousand-fold in process known as activation. Once
their job is complete, T-cells are eliminated in a process
known as apoptosis. While caspase-8 is largely recognized
as a critical factor in this elimination process, this study
produced a new finding: caspase-8 is also essential for
the activation of T-cells at the start of the immune response.
"This
research has helped us better understand how caspase-8 activates
the immune system response by triggering T-cells to proliferate.
When caspase-8 is inhibited, the immune response is significantly
decreased," explains Dr. Razqallah Hakem, principal
investigator AMDI/OCI and Assistant Professor in Medical
Biophysics at the University of Toronto.
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The
research builds on findings published last fall in Nature, which
revealed that caspase-8 mutations are linked to immunodeficiency
in humans. But the in vivo role of caspase-8 has remained uncertain
until now, because deleting the molecule is lethal to embryos-making
it impossible to fully understand what happens to cells without
the molecule.
Researchers
overcame this hurdle by targeting and eliminating caspase-8 from
specific organ tissues in mice, enabling them to see how these
tissues are affected by the absence of caspase-8.
"The research we've done has created a unique
model that we and other scientists can use to further study the role
of caspase-8 in the immune response," reports AMDI researcher
and lead author of the study, Leonardo Salmena, who is a PhD candidate
in Medical Biophysics at the University of Toronto.
Understanding how caspase-8 operates in T-cell proliferation
and activation is an important first step towards understanding immune
system abnormalities and how these processes might be controlled to
treat overactive immune systems. Researchers hope that continued research
could impact therapies for autoimmune disorders such as lupus, multiple
sclerosis, and Type I diabetes.
The research was supported by Amgen Incorporated,
and by grants from the Canadian Institute of Health Research, and
the National Cancer Institute of Canada.
This story has been adapted from a news release issued
by University Of Toronto, www.utoronto.ca.
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