Why is the immune system able to fight off some viruses

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ScienceDaily (May 10, 2009) — Why is the immune system able to fight off some

viruses but not others, leading to chronic, life-threatening infections like HIV

and hepatitis C?

A new UCLA AIDS Institute study suggests the answer lies in a protein called

interleukin-21 (IL-21), a powerful molecule released by immune cells during

chronic infection. Published May 7 in the online edition of Science, the finding

could explain how the immune system limits viral replication, restricting a

virus's spread through the body.

The researchers looked at two types of T-cells — CD4 T-cells and CD8 T-cells —

which are immune cells that play an important role in the body's response to

infection. The CD4 T-cells help the immune system by producing IL-21 during

chronic infection, bolstering the CD8 T-cells' ability to fight off the virus.

" The CD4 cells are the regulators — the generals, if you will, " said principal

investigator , assistant professor of microbiology, immunology and

molecular genetics at the Geffen School of Medicine at UCLA. " The CD8

cells go out and kill the invaders; they're like the privates in the field. "

To shed light on how CD4 T-cells help their CD8 counterparts clear viruses, the

researchers infected mice with one of two strains of a virus. They knew that the

first strain would generate a short-term infection and the second a chronic

infection.

The scientists tested each strain on two groups of mice. One group was normal

and the other was bred without IL-21 receptors.

In the normal mice, the first strain elicited a strong T-cell response that

completely eliminated the virus in 10 days. The second strain caused a chronic

infection that exhausted the T-cells, hampering their ability to fight the

virus. The UCLA team detected high levels of IL-21 in these mice, suggesting

that the protein plays a crucial role in sustaining the T-cells' ability to

mount an immune response during long-lasting infection.

When the scientists infected the mice that lacked IL-21 receptors with the

chronic infection strain, something curious happened. The majority of

virus-fighting CD8 T-cells disappeared, preventing the immune system from

containing the spread of the virus.

" IL-21 fuels CD8 T-cells' ability to function, " 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. "

Without IL-21, the CD8 T-cells dwindled, even when the CD4 T-cells produced a

robust response. The result indicates that the T-cells rely on IL-21 to resolve

persistent infection.

" After the immune system loses CD8 T-cells, it's unable to clear the virus, "

said. " This tells us that IL-21 is a critical player in the body's fight

against chronic infection. "

The study was funded by the UCLA Center for AIDS Research, the Eli and Edythe

Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, and the

National Institutes of Health. ' co-authors included Heidi Elsaesser of

UCLA and Karsten Sauer of the Scripps Research Institute.