AIDS Researchers Found Molecular Switch that Turns off Immune Cells – HIV Exhausts Killer T-cells

AIDS Researchers Found Molecular Switch that Turns off Immune Cells – HIV Exhausts Killer T-cells

In an international effort, researchers have found that a molecular switch or pathway is “turned off” in people with AIDS, which prevents the immune system from removing the virus. One of the mysteries involved in the search for a cure for AIDS has been the CD8 cells that don’t seem to be doing their jobs in AIDS patients.

According to Doctor Bruce Walker, “Back in 1987 our MGH team confirmed the existence of HIV-specific CD8 cells, the cytotoxic T lymphoctyes that should destroy virus-infected cells. But it didn't make sense that these cells were found in high numbers in persons with late-stage disease (AIDS), indicating that they were somehow not doing their job. These new findings finally make sense out of our early discoveries and subsequent findings by others in the field: The immune cells are there, but they have been turned off in persons with high viral loads." Walker is director of the Partners AIDS Research Center (PARC) and principal investigator of the Nature study.

Previous studies have shown that a molecular pathway involving a receptor, called PD-1 (Programmed Death-1), inhibits the immune system in chronic viral infections. Initially the CD8 cells respond to viral infections by reproducing dramatically and producing cytokines that help destroy the viruses. The researchers say that the same pathway also plays a role in other chronic viral infections.

To examine whether antiviral therapy might change the expression of PD-1, the researchers examined blood samples taken from four HIV-positive participants before and after they began antiretroviral therapy. Along with the expected drop in viral load in response to treatment, there was also a significant decrease in PD-1 expression on HIV-specific CD8 cells, suggesting that elevated receptor expression may be a response to the high viral loads of untreated individuals.

Using antibodies to block the PD-1 pathway in blood cells from infected individuals significantly increased the ability of HIV-specific CD8 cells to proliferate in response to viral antigens and also increased the cells' production of the cytokine gamma interferon, indicating improved function. Blocking the PD-1 pathway also increased the proliferation of HIV-specific CD4 cells, and even cells from individuals that previously had no detectable response had robust proliferation after pathway blockade, indicated that cells that had been turned off could be turned back on.

The research will be published in an upcoming issue of the journal Nature. The paper from researchers at the Partners AIDS Research Center at Massachusetts General Hospital (MGH), the University of KwaZulu-Natal (UKZN) in South Africa, and other institutions has received early online publication.

By Marsh Quinn
Best Syndication Staff Writer



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