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Wily HIV Attacks Body's Palace Guard

Knocks out immune cells that mark it for destruction

WEDNESDAY, May 1, 2002 (HealthDayNews) -- A new study, confirming what AIDS researchers have long suspected, says that the deadly virus takes out the very immune cells primed to recognize the infection.

A team of scientists led by government researchers has found that HIV preferentially destroys the so-called CD4 T cells programmed to mark the microbe for destruction. At the same time, HIV causes less damage to T cells dedicated to other organisms.

CD4 T cells help the immune system launch an attack against invaders -- earning them the nickname "helper" cells. So the AIDS virus has in effect figured out a way to topple the body's immune infrastructure by knocking out its keystone.

Although a bit of basic research, the finding, reported in today's issue of the journal Nature, could have major implications for HIV treatment, experts said. Scientists are now investigating therapies that give patients brief "drug holidays" designed to startle the immune system and reduce side effects from highly toxic antiviral drugs.

But Dr. Daniel Douek, an AIDS researcher at the National Institute of Allergy and Infectious Diseases and lead author of the Nature study, said the latest work undermines the logic of that approach.

"The idea [with drug holidays] is that the rebound of virus would boost the immune response against the virus. But at the same time that's happening you're infecting the CD4 cells. It's robbing Peter to pay Paul." The researchers saw that in four patients in whom HIV drugs were temporarily suspended, virus levels spiked -- as did HIV-specific CD4 cells, giving the microbe more opportunities to infect.

On the other hand, Douek said, the results suggest that an alternative tack -- pausing therapy for a week to ease its toxicity but not long enough to let the virus damage the immune system -- may be successful.

One of the early discoveries in HIV research was that people infected with the virus lose HIV-specific CD4 cells as their disease progressed. Why that was true wasn't clear, but scientists speculated that the organism selectively attacked and killed off these cells over time. Since the body's killer T cells (called CD8s), which rely on helper cells for instructions on what to attack, aren't susceptible to HIV, destroying CD4 cells was a clever way for the pathogen to erode the entire immune system downstream.

This model of HIV, while likely, couldn't be proved until only recently because the technology hadn't caught up to the theory. Yet relatively recent advances allowed Douek and his colleagues in Israel and the United Kingdom to study CD4 cells in 12 people infected with HIV. To do so, they screened massive amounts of white blood cells, looking for signs of viral DNA in the CD4 cells that are a component of these immune agents.

As expected, HIV genetic material was about four times more likely, on average, to be present in HIV-specific T cells than in those specific to other microbes -- including cytomegalovirus, a common infection in AIDS patients -- or which hadn't yet been dedicated.

The body has so vast a repertoire of CD4 cells, numbering in the many trillions, that it's believed to encompass every potential infectious threat.

"According to classical immunology, you don't generate good anti-HIV CD8 cell and antibody response [antibodies are immune proteins that help rally defenses against infection]" without a solid anti-HIV CD4 supply, Douek said. "You need them to fight the virus. The trouble is, they're getting infected."

Dr. Howard Grossman, a private AIDS specialist in New York City, said the latest study won't change his clinical practice. But "it's nice to know that they've proved something they've been talking about for a long time."

The role of CD4 cells and HIV still contains a major mystery, Grossman added. Some patients with the virus can live for years with a healthy count of the T cells and not progress to full-blown AIDS.

What To Do

More than 40 million people worldwide are believed to be infected with HIV, according to the Centers for Disease Control and Prevention. In the United States, nearly 800,000 people had been diagnosed with AIDS through June of last year.

For more on the disease, try the CDC or the National Institute of Allergy and Infectious Diseases.

SOURCES: Daniel Douek, M.D., Ph.D., chief, human immunology section, vaccine research center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.; Howard Grossman, M.D., Polari Medical Group, New York City; May 2, 2002 Nature
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