Key Protein Contains Chronic Infection

A research team from UCLA, led by Prof. David Brooks has discovered the reason why the immune system can fight off some infections and surrenders to others. This discovery, say the scientists, may help them develop drugs that fight chronic infections such as Hepatitis C and AIDS.
 T-cell (Credit: UC Berkeley Lab)
T-cell (Credit: UC Berkeley Lab)

T-cells play an important role in the human immune system as some of them stimulate the immune response to an infection. In the current experiment, the researchers investigated two types of T-cells : CD4 T-cells and CD8 T-cells. CD4 cells produce a substance called IL-21 as part of an immune response to a chronic infection, which helps the body fight the virus and increases the CD8 T-cells’ ability to attack the invading virus.

“The CD4 cells are the regulators — the generals, if you will,” said principal investigator David Brooks, assistant professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA. “The CD8 cells go out and kill the invaders; they’re like the privates in the field.”

In order to understand the exact process by which the CD4 cells aid the CD8 in fighting off viruses, the researchers infected mice with two strains of a virus. The first strain was intended to elicit a short term infection in the mice, while the second generated a chronic infection. The scientists tested each strain on two groups of mice – one of the groups was normal and the other was genetically modified to not have the IL-21 receptor.

Some of the results were straightforward: in the normal mice, the first virus strain was completely eliminated by a strong T-cell response. The second strain caused a chronic infection which exhausted the T-cells and compromised their ability to fight the virus. The researchers measured high levels of IL-21 in these mice, which suggested that the protein plays an important role in the T-cells’ ability to sustain an immune response during long lasting infection.

 Principal investigator David Brooks, UCLA assistant professor of microbiology, immunology and molecular genetics (Credit: UCLA)
Principal investigator David Brooks,
UCLA assistant professor of
microbiology, immunology and
molecular genetics (Credit: UCLA)

However, when the scientists infected the genetically modified mice with the chronic infection strain, they were in for a surprise. The majority of the CD8 “privates” disappeared and the immune system failed in the attempt to contain the spread of the virus. “IL-21 fuels CD8 T-cells’ ability to function,” Brooks explained. “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.”

When IL-21 doesn’t bind to the CD8 cells, their population dwindles, even though CD4 cells are trying to recruit them in full speed. These results indicate that the T-cells depend on IL-21 to fight off a persistent infection. “After the immune system loses CD8 T-cells, it’s unable to clear the virus,” Brooks said. “This tells us that IL-21 is a critical player in the body’s fight against chronic infection.”

The possibility to affect the production of IL-21 by external manipulations opens up a new angle for fighting chronic diseases. If scientists succeed to turn this knowledge into a drug, it would revolutionize our fight against chronic infections such as AIDS and Hepatitis C.

TFOT has previously brought you a story on the research of receptors in connection to HIV, conducted by scientists from Cornell University. We’ve also covered the identification of a gene that may influence the production of antibodies that neutralize HIV, discovered at the Gladstone Institute of Virology and Immunology.

For more information on the protein please visit the UCLA university newsroom.