Interferon Needed For Cells To 'Remember' How To Defeat A Virus

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http://www.sciencedaily.com/releases/2008/12/081203084316.htm

Interferon Needed For Cells To 'Remember' How To Defeat A Virus

ScienceDaily (Dec. 8, 2008) — Scientists at UT Southwestern Medical Center have

determined that the immune-system protein interferon plays a key role in

" teaching " the immune system how to fight off repeated infections of the same

virus.The findings have potential application in the development of more

effective vaccines and anti-viral therapies.

Typically, when a person is infected with a virus, the human body immediately

generates a massive number of T cells – a type of immune cell – that kill off

the infected cells. Once the infection has cleared, most of the T cells also die

off, leaving behind a small pool of central memory cells that " remember " how to

fight that particular type of virus if the person is infected again.

" In this study, we have uncovered interferon's role and the key signaling

protein, called IL-2, involved in generating memory T cells, " said Dr.

Farrar, assistant professor of immunology at UT Southwestern and senior author

of the study. " Knowing how T cells acquire this memory may help us design better

strategies and vaccines to fight HIV and other infectious diseases. Further, our

discovery was made using primary human CD4+ T cells, which underscores the

relevance of our discovery to human immune responses. "

CD4+ T cells coordinate the actions of other cells at the site of infection.

When a virus or bacterium infects a human, the infected cells secrete several

molecules, including a cytokine – or signaling protein – called interferon

alpha. The action of interferon is what makes an infected person feel run down

and tired. Although scientists knew that interferon alpha prevented a virus from

multiplying and spreading, they didn't know what role interferon played in the

creation of memory cells.

In the current study, the UT Southwestern researchers show that both interferon

alpha and another signaling protein called IL-12 are needed to induce the

creation of memory cells. They found that interferon and IL-12 team up to

promote the creation of a special set of cells that then secrete another

signaling protein called IL-2. These IL-2-secreting cells are the ones that

remain in the body and " remember " how to fight off the virus.

" Without the IL-2 signaling protein, you'll generate a beautiful primary

response against a virus, and you'll eliminate the bug, but your body won't

remember how it defeated the virus, " Dr. Farrar said. " Without these memory

cells, your body is defenseless against re-infections. "

Ann , student research assistant in immunology and lead author of the

study, said this suggests a new role for interferon: teacher.

" This is really the first demonstration of a role for interferon in teaching a T

cell how to respond to viral infections, " she said.

Dr. Farrar added: " Up until now, interferon has always been appreciated for its

role in inhibiting virus infections. But no one's really paid attention to

interferon and its role in regulating memory. That's why we're so excited about

this result. "

The next step, Dr. Farrar said, is to complete the same study in mice. Early

results show that mice with T cells that can't respond to interferon are unable

to protect themselves when a virus invades.

" Their immune systems have no idea how to fight the virus, " Dr. Farrar said. Dr.

Farrar said these early findings in mice may pave the way for designing more

effective vaccines.

This research is available online and in the Dec. 15 issue of the Journal of

Immunology. Other UT Southwestern researchers involved in the study were Hilario

Ramos, student research assistant in immunology, and Dr. Laurie , associate

professor of internal medicine.

The National Institutes of Health supported the research.

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Adapted from materials provided by UT Southwestern Medical Center.