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Immune response depends on key molecule: Research

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.

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 resear
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Contact: Kim Garwood
kim.garwood@uhn.on.ca
416-340-4800 Ext. 6753
University of Toronto
31-Mar-2003


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