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Pivotal protein keeps chronic infections contained
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Common sense supports the theory that in order to defeat a disease, one must first understand how the immune system works against it. But as immune response is one of the most complex systems in the human body, the story of how it works is still plagued by inconsistencies and plot holes. One void in particular, how the body is able to completely eradicate some viruses while others persist into chronic infections, is poorly characterized.
David Brooks, assistant professor at the David Geffen School of Medicine at UCLA, conducted a set of experiments to investigate how the body deals with long-term infection. His team studied two immune cell types, CD4 and CD8. During infection, CD4 cells produce a protein called interleukin-21 (IL-21), which recruits and promotes CD8 cells’ ability to battle and contain the virus.
In order to understand the role IL-21 plays in immune response, Brooks created an IL-21 receptor knockout mouse line. These mice lack IL-21 receptors, meaning even if CD4 cells were producing IL-21, the CD8 cells would not be able to recognize and react to it. They then tested two strains of a virus, one that causes short-term infection and one that is known to become chronic.
The normal, non-knockout mice responded in a predictable way. The first virus was completely cleared after a short time, and the second caused immune system-exhausting chronic infection. The researchers found elevated levels of IL-21 in the second case, “suggesting that the protein plays a crucial role in sustaining the T-cells' ability to mount an immune response during long-lasting infection.” [EurekAlert]
However, the chronic infection invoked a different reaction in the knockout mice. As the infection wore on, most of the CD8 cells disappeared, allowing the virus to spread throughout the body. Without the IL-21 receptors, these cells weren’t able to continue the fight. "IL-21 fuels CD8 T-cells' ability to function," Brooks said. "These immune cells are running a long-distance race to contain the virus before it spreads. If they don't get fed, they collapse on the track." [EurekAlert]
With the knowledge that IL-21 is an essential soldier in the fight against chronic infection, researchers can investigate whether an irregularity in the protein or its receptor may cause complications in long-term infections such as HIV or hepatitis C, perhaps creating more effective therapies to battle the diseases.
This study was published in a recent issue of Science.
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