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Research breakthrough- PD-1 protein and restarting immune system.

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J220:
From New Scientist...I know this is "old" - a month ago, and it was also posted at the news section here- but fantastic news nontheless. They may have hit on the most important biochemical target that may in fact lead to a cure. If scientists can find a way to suppress PD-1, without causing autoimmune problems, then CD8 cells could reawaken and complete the job of killing hiv-infected cells in the system. It's encouraging that researchers recognize the importance of this discovery and want to begin clinical trials as soon as possible.


Detailed studies of white blood cells have revealed how HIV relentlessly wears down the immune cells by exploiting the body’s built-in protection against autoimmune diseases. The new understanding should lead to ways to overcome this "Achilles heel" and treat HIV infection.

As HIV accumulates in the blood, specific immune cells that target viruses – called CD8 – begin to over-produce a receptor molecule called Programmed Death-1. As this PD-1 builds up on the surface of the CD8 cells, the immune cells became weaker and produced fewer virus-killing chemicals, such as cytokines.

Instead of functioning as sentinels of the immune system, the CD8 cells gradually burn out, becoming clogged-up with PD-1. “The immune cells are there, but they have been turned off in persons with high viral loads,” says Bruce Walker at Massachusetts General Hospital in Boston, US, who led the research.

Tandem changes

The biological function of PD-1 is not fully understood, but it is thought that it may be involved in preventing autoimmune reactions – where the white blood cells attack the body’s own cells.

Walker and his collaborators examined CD8 cells from 71 untreated HIV-positive patients in Durban, South Africa. They found that the more virus the patients had in their bodies, the more PD-1 they had on their CD8 cell surfaces.

But when Walker massively suppressed the amount of virus circulating in their blood by giving the patients antiretroviral drugs, the amount of PD-1 on their CD8 cells went down too, suggesting that the two rise and fall in tandem.

The same phenomenon was demonstrated in 19 North American individuals by a team led by Rafick-Pierre Sekaly at the Central Hospital of Montreal in Canada.

Mutual confirmation

In lab experiments, though, Sekaly showed that even after antiretroviral drugs were given, the CD8 cells continued to weaken despite the fact that the drugs drove down the amount of PD-1. “The drugs didn’t correct the dysfunction, and the cells got more and more tired and burnt out,” he says.

But the two teams were able to help the cells to recover using antibodies that block the PD-1 receptor molecules. In cell culture, these CD8 cells resumed their normal activity when exposed to HIV, producing chemicals such as interferon gamma, for example, which targets viruses including HIV.

And experiments in mice treated with similar antibodies also blocked the production of PD-1.

The teams, whose results were both published at the same time, in the journals Nature and Nature Medicine respectively, are delighted that each others' findings have been mutually confirmed.

Now, Sekaly wants to try the same thing in people. “We need to start a clinical trial as soon as possible,” he says.

Total block

Sarah Rowland-Jones, director of research at the UK Medical Research Council’s Labs in Fajara, Gambia, says that it would be interesting to know if the virus itself somehow triggers the CD8 cells to overproduce PD-1. “It wouldn’t surprise me in the slightest,” she says.

However, Rowland-Jones, who wrote a commentary piece accompanying the two studies, in Nature, warns that blocking PD-1 altogether could be dangerous. She says that in experiments on mice bred to lack the gene, the mice developed severe autoimmune disease.

This suggests that the protein plays an important role in stopping the immune system attacking itself. Perhaps, she says, HIV exploits this to blind the immune system to its presence.

Journal references: Nature (DOI: 10.1038/nature05115), Nature Medicine (DOI: 10.1038/nm1482)

J220:
I wrote to Dr. Walker and he responded, among other thigns he said that they are "cautiously encouraged" by their findings, but he does say that they still have a long way to go. He did mention that they have some international partnerships that are a key element in fighting hiv- he's in South Africa right now.

All in all, very encouraging to see that they are working hard, and making important progress....we'll get there you'll see! J.

Arkan:
There are some natural compounds that seem to block PD-1... there is much more to that article. Do you wonder why the current meds do not restore CD8?
I found a large number of essays on the same issue and more extensive documentation on how the immune system could be reactivated. The author of this web page has placed all the information together and proposing a mechanism to fight back HIV based in part to what you posted.

Check it out at http://www.grouppekurosawa.com

IT WORKS!! I am alive and getting stronger everyday!

Best to all!

Gus

thirtysomething:
I think that website looks like another money-making scheme by selling Vitamins..

Arkan:
I really can't see what part is the money making  :)  may be you should check the disclaimer in that web page, then compare to any conventional anti-retroviral therapy and see all the interests behind keeping the drugs in the market (now that's money making!!).
Only time and brave people will prove them right or wrong. In the mean time the website successfully and well funded present and alternative to conventional therapies. We need alternatives, because after 25 years we have not solved the HIV problem.
Good luck to all!!

G

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