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'Pep talk' can revive immune cells exhausted by chronic viral infection
Date:12/13/2011

Chronic infections by viruses such as HIV or hepatitis C eventually take hold because they wear the immune system out, a phenomenon immunologists describe as exhaustion.

Yet exhausted immune cells can be revived after the introduction of fresh cells that act like coaches giving a pep talk, researchers at Emory Vaccine Center have found. Their findings provide support for an emerging strategy for treating chronic infections: infusing immune cells back into patients after a period of conditioning.

The results are published this week in Proceedings of the National Academy of Sciences Early Edition.

The first author of the paper is Rachael Aubert, a student in Emory's Immunology and Molecular Pathogenesis program who completed her doctorate in 2009. Senior author Rafi Ahmed, PhD, is director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.

Ahmed's laboratory has extensive experience studying mice infected with lymphocytic choriomeningitis virus (LCMV). Immune responses against LCMV are driven by CD8 or "killer" T cells, which destroy virus-infected cells in the body. But a few weeks after exposure to LCMV, the mice develop a chronic infection that their immune systems cannot shake off, similar to when humans are infected by viruses like HIV and hepatitis C.

Aubert and her co-workers examined what happened to mice chronically infected with LCMV when they infused CD4 or "helper" T cells from uninfected mice. After the infusion, the CD8 cells in the infected mice revived and the levels of virus in their bodies decreased by a factor of four after a month. Like coaches encouraging a tired athlete, the helper cells drove the killer cells that were already in the infected mice to emerge from exhaustion and re-engage.

The cell-based treatment was especially effective when combined with an antibody that blocks the molecule PD-1, which appears on exhausted T cells and inhibits their functioning
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

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