UdeM researchers find key to reviving immune system
’Not just relevant to HIV’;’ Results raise exciting possibility that doctors could have new tool to fight diseases
**CHARLIE FIDELMAN, The Gazette Published: Wednesday, August 23, 2006 **
A Montreal immunology team has announced a breakthrough discovery of a key component that has baffled scientists in the fight against the AIDS epidemic.
What’s more, the researchers say they have found a way to reawaken an exhausted immune system to fight HIV again.
The mystery: Why is the immune system not able to get rid of HIV-infected cells?
The answer, Universite de Montreal lead investigator Rafick-Pierre Sekaly said, is that CD8 T cells, which kill viral infections, become exhausted and quit functioning in HIV patients. “We have discovered the mechanism that the virus is exploiting to undermine the immune system and make it completely dysfunctional.”
"Most important, we have shown that this can be reversed.
“We can correct this defect, and this, for us, gives us great hope because a lot of other strategies have always failed.”
The findings raise the exciting possibility that doctors could one day manipulate a patient’s immune system into switching back on to fight HIV, cancer and infectious diseases.
Virologist Mark Wainberg, director of the McGill AIDS Centre at the Jewish General Hospital, who was not involved in the study, called the breakthrough much broader than HIV.
“It’s not just relevant to HIV but to immunodeficiency in other disease states,” he said.
Sekaly’s team, which published its finding in the journal Nature Medicine, is heartened that two other teams, led by Bruce Walker of Harvard Medical School and Richard Koup at the U.S. National Institutes of Health, simultaneously produced similar results.
“All of us came to the same conclusion - it’s a rare occurrence for three teams,” said Sekaly, who worked with a group at the Royal Victoria Hospital led by McGill University Health Centre HIV/AIDS expert Jean-Pierre Routy.
“For us, it’s the first evidence that the HIV default can be reversed in the laboratory,” Routy said.
The Harvard, NIH and Montreal teams reported that blocking a molecule called PD1 (programmed death-1) restored the function of the T cells.
While this worked against a chronic infection in mice, it’s more than just another complex animal model, Routy added. “This blockade of an (overworking) gene leads to the clearance of the infection,” he said.
PD1 inhibits the function of the T cells, Sekaly explained.
“We’ve shown that you can reverse the course of infection by waking up the immune system,” he said. “A lot of other strategies have failed, but now we can restore the function of CD8 cells and, therefore, the immune system.”
But tinkering with the immune system to switch it back on is risky because it could trigger autoimmune disease, experts cautioned.
“The danger is that you could have a real overdrive,” Sekaly said, commenting on a botched London trial of a drug to stimulate the immune system; in March, six healthy volunteer men landed in intensive care “suffering from severe respiratory distress,” he said.
cfidelman@thegazette.canwest.com
ONLINE EXTRA: Twenty-five years after health officials first recognized the disease that became known as AIDS, the virus is no longer synonymous with terminal illness. montrealgazette.com
[CENTER]© The Gazette (Montreal) 2006
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**forgot to put the source… **http://www.canada.com/montrealgazette/news/story.html?id=88738959-8a26-4641-890c-1ffb54414891
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[LEFT]this is just amazing!!! Yay go Montreal I love my city! :} [/LEFT]
