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Molecular switch may turn off immune cells that target HIV

One of the primary mysteries of the AIDS epidemic why the immune system is unable to control HIV infection may have been solved by an international research collaborative. In an upcoming issue of Nature, the team reports how a molecular pathway involved in the immune cell "exhaustion" that characterizes several other chronic viral infections plays a similar role in HIV infection. They also found that blocking the pathway restores some function to HIV-specific CD8 and CD4 T cells. 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.

"Back in 1987 our MGH team confirmed the existence of HIV-specific CD8 cells, the cytotoxic T lymphoctyes that should destroy virus-infected cells," says Bruce Walker, MD, director of the Partners AIDS Research Center (PARC) and principal investigator of the Nature study. "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."

Several recent studies have shown that a molecular pathway involving a receptor called PD-1 (Programmed Death-1) inhibits the immune system in chronic viral infections those in which the immune system does not completely clear the virus. CD8 cells initially respond to viral infection by reproducing dramatically and producing cytokines that help destroy the viruses, but in chronic infection high levels of virus appear to overwhelm and exhaust CD8 cells. Recent studies in mice by Rafi Ahmed, PhD, of Emory University School of Medicine and Gordon Freeman, PhD, of Dana-Farber Cancer Institute both co-aut
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
20-Aug-2006


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