Immune exhaustion driven by antigen in chronic viral infection

May 13, 2009

A main reason why viruses such as HIV or hepatitis C persist despite a vigorous initial immune response is exhaustion. The T cells, or white blood cells, fighting a chronic infection eventually wear out.

Researchers at Emory Vaccine Center have demonstrated that exhaustion is driven by how the immune system detects infecting viruses.

To recognize the presence of a viral infection, T must be presented with bits of viral protein in a molecular frame supplied by other cells in the body -- called MHC (major histocompatibility complex) class I molecules.

In mice infected by lymphocytic choriomeningitis virus (LCMV), became more or less exhausted depending on how much properly framed viral protein was available.

Insights from the research could guide efforts to revive the immune system in people with chronic viral infections. The results are published online this week in the Proceedings of the National Academy of Sciences.

Working with Vaccine Center director Rafi Ahmed, PhD, postdoctoral fellow Scott Mueller, PhD, examined the effects of limiting what kind of cells could display the viral antigens.

Ahmed is professor of microbiology and immunology at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar.

By performing bone marrow transplants on genetically engineered mice, Mueller created mice with MHC class I molecules on blood and immune system cells but missing from other cells such as and connective tissue. LCMV infects both cells that come from bone marrow and cells that don't. But the roles each type of cell plays in communicating the infection to the immune system is different.

"We were trying to sort out which of several factors contribute to T cell exhaustion, such as viral antigen, inflammation and where the immune system encounters the virus," Mueller says. "What came out of these experiments allowed us to answer a broad question: the role of antigen in driving exhaustion."

When injected with LCMV, the altered mice had more energetic and responsive T cells early during the infection. But later, the altered mice had much higher levels of virus and more exhausted T cells. This contrast demonstrates how the level of antigen present is the motor behind immune exhaustion during the chronic infection.

"Early on, the T cells were healthier because they saw less antigen, and only saw it on cells that came from ," Mueller says. "But later, the had trouble getting rid of the virus because the T cells couldn't recognize infection in cells that were not able to present the viral antigens."

Source: Emory University (news : web)

Related Stories

Recommended for you

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

New breast cell types discovered by multidisciplinary research team

November 20, 2017
A joint effort by breast cancer researchers and bioinformaticians has provided new insights into the molecular changes that drive breast development.

Brain cell advance brings hope for Creutzfeldt-Jakob disease

November 20, 2017
Scientists have developed a new system to study Creutzfeldt-Jakob disease in the laboratory, paving the way for research to find treatments for the fatal brain disorder.

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

Age and gut bacteria contribute to multiple sclerosis disease progression

November 17, 2017
Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to multiple sclerosis (MS) disease onset and progression.

Molecular guardian defends cells, organs against excess cholesterol

November 16, 2017
A team of researchers at the Harvard T. H. Chan School of Public Health has illuminated a critical player in cholesterol metabolism that acts as a molecular guardian in cells to help maintain cholesterol levels within a safe, ...

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.