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Study Investigates Technique for Improving Immune Responses to Chronic Viral Infections

Researchers at the Dana Farber Cancer Institute in Boston, MA and Emory University in Atlanta, GA recently investigated why particular cells stop fighting chronic viral infections. The study focused on CD8 T cells, a key component of the body’s immune system known for fighting viral infections such as HIV and hepatitis. “CD8 T cells that have fought viral infections retain a ‘memory’ of the viruses they’ve encountered, so they can rapidly respond to new infections from those viruses,” according to study author Gordon Freeman, PhD of Dana Farber. Although these cells are important, at a certain point CD8 T cells often lose the impetus to continue resisting infection, become “exhausted,” and ultimately ineffective. Researchers at Dana Farber appear to have pinpointed a potential genetic trigger for this response.

Using mice, scientists measured the activity of thousands of genes in both normal CD8 T cells and exhausted versions. Findings revealed that the gene PD-1 was significantly more active in the exhausted CD8 T cells. Specifically, it was discovered that PD-1, which is responsible for receptors (receivers of signals from other cells) in CD8 T cells, connects with the molecule PD-L1 to inhibit anti-viral functioning. Dr. Freeman and his colleagues discovered this causative interaction and subsequent way to revive CD8 T cell efficacy. “We found that exhausted CD8 T cells in mice have unusually large numbers of PD-1 receptors, and blocking the PD-1/PD-L1 bond reactivated the cell’s response to infection.”

Dr. Freeman has also been able to produce antibodies to obstruct PD-1/PD-L1 interaction. Since CD8 T cells operate similarly in humans to the way they do in mice, researchers hope to find a new mode of treatment for patients with chronic viral infections. Dr. Freeman and his colleagues recently received a grant from the Bill and Melinda Gates Foundation’s Grand Challenges in Global Health program to study their research applications to hepatitis C virus infection.

The study was published online on December 28, 2005 by the journal Nature.

Source: Medical Science News, December 29, 2005


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