'Pep talk' can revive immune cells exhausted by chronic viral infection

December 13, 2011, Emory University

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 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 : infusing immune cells back into patients after a period of conditioning.

The results are published this week in 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" , 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 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. The antibody against PD-1 helps the exhausted T cells to revive, and enhances the function of the helper cells as well: the combination reduced viral levels by roughly ten-fold, and made the virus undetectable in some mice.

"We have not seen this sharp of a reduction in viral levels in this system before," says co-author Alice Kamphorst, a postdoctoral fellow.

The helper cells were all genetically engineered to recognize LCMV, a difference between mouse experiments and potential clinical application. However, it may be possible to remove helper T cells from a human patient and stimulate them so that all the cells that recognize a given virus grow, Kamphorst says.

"This is an active area of research and several laboratories are looking at how best to stimulate T cells and re-introduce them," she says.

In addition, she and her co-workers are examining what types of hormones or signaling molecules the helper cells provide the . That way, that molecule could be provided directly, instead of cell therapy, she says.

The molecule PD-1 was previously identified by Ahmed and colleagues as a target for therapy designed to re-activate exhausted immune cells. Antibodies against PD-1 have been undergoing tests in clinical studies against and several forms of cancer.

Explore further: Strengthening fragile immune memories to fight chronic infections

More information: R.D. Aubert et al. Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection. PNAS Early Edition (2011).

Related Stories

Strengthening fragile immune memories to fight chronic infections

August 18, 2011
After recovering from the flu or another acute infection, your immune system is ready to react quickly if you run into the same virus again. White blood cells called memory T cells develop during the infection and help the ...

Recommended for you

LincRNAs identified in human fat tissue

June 21, 2018
A large team of researchers from the U.S. and China has succeeded in identifying a number of RNA fragments found in human fat tissue. In their paper published in the journal Science Translational Medicine the group describes ...

Scientists solve the case of the missing subplate, with wide implications for brain science

June 21, 2018
The disappearance of an entire brain region should be cause for concern. Yet, for decades scientists have calmly maintained that one brain area, the subplate, simply vanishes during the course of human development. Recently, ...

Key molecule of aging discovered

June 21, 2018
Every cell and every organism ages sooner or later. But why is this so? Scientists at the German Cancer Research Center in Heidelberg have now discovered for the first time a protein that represents a central switching point ...

Compound made inside human body stops viruses from replicating

June 20, 2018
The newest antiviral drugs could take advantage of a compound made not by humans, but inside them. A team of researchers has identified the mode of action of viperin, a naturally occurring enzyme in humans and other mammals ...

Research reveals zero proof probiotics can ease your anxiety

June 20, 2018
If you're expecting probiotics to reduce your anxiety, it might be time to put down that yogurt spoon—or supplement bottle—and call a professional instead.

Long-term estrogen therapy changes microbial activity in the gut, study finds

June 20, 2018
Long-term therapy with estrogen and bazedoxifene alters the microbial composition and activity in the gut, affecting how estrogen is metabolized, a new study in mice found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.