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Immune System Memory Center Identified

Finding could lead to better vaccines, cancer treatments

THURSDAY, April 22, 2004 (HealthDayNews) -- In a discovery that could lead to more effective vaccines and better treatments for cancer, researchers have identified a protein that enables immune system cells to retain a memory of enemies past.

The protein is found in T cells, which pick up the foreign antigens of viruses or bacteria that invade the body. The T cells multiply, sending signals that foster production of B cells, which make antibodies that attack and destroy the invaders.

Once the T cells have done their job, most -- but not all -- of them die away. A small number of "memory" T cells are preserved, however, ready to rally a quick response should the infectious agent return.

Until now, the molecular mechanism behind that memory has been unknown. But a group led by Hilde Cheroutre, an associate member of the La Jolla Institute for Allergy and Immunology in San Diego, reports in the April 23 issue of the journal Science that the mystery memory molecule is a form of a protein called CD8.

More accurately, CD8 consists of a dimmer -- two closely linked proteins dubbed alpha and beta. Most T cells make an alpha-beta CD8. A few make an alpha-alpha version. Those are the ones that become memory cells, Cheroutre said.

"We've wondered about alpha-alpha for a long time, because it is less efficient in the function we knew about it, helping T cells become activated," Cheroutre said. "Now we have defined a different function. It slows down T cells. As they kill invading cells, they also die themselves. Alpha-alpha CD8 allows the immune system to select the best soldiers and save them for later."

Dr. Dan R. Littman is a professor of molecular immunology at New York University Medical Center, who has long done research on T cells and participated in the new discovery. "We have a lot we can do with this finding," he said.

One obvious end product is a vaccine that reacts more quickly, he said.

"Once we understand how CD8 controls the memory response, instead of setting aside, say, 2 percent of the T cells as memory cells, maybe we set aside 10 percent and get a better response," Littman said.

Cheroutre sees improved vaccines as just one of several possibilities.

"It [alpha-alpha] is an indicator of how good the immune system memory is," she said. "If a vaccine produces a lot of alpha-alpha cells, it is an effective vaccine."

To improve treatment of an infection, "alpha-alpha can be used as a marker to isolate T cells from a patient," Cheroutre said. "We can give those cells back to the patient, expanding the immune system memory so the patient is more protected."

The same strategy might be used to help the immune system fight cancer, she said, by isolating T cells that are most aggressive in attacking tumors.

Efforts to exploit the finding are continuing on both coasts, Littman said.

"What we are doing now is trying to find out how the gene for alpha CD8 is regulated," he said.

More information

For more on vaccines, visit the National Institutes of Allergy and Infectious Diseases.

SOURCES: Hilde Cheroutre, Ph.D, associate member, La Jolla Institute for Allergy and Immunology, San Diego; Dan R. Littman, M.D., Ph.D., professor of molecular immunology, New York University Medical Center, New York City; April 23, 2004, Science
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