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Protective gene may enhance vaccine responses

Researchers from the University of Chicago have discovered the first of a new class of "protective factors" that appear to be required for the development of memory T cells, the cells that form the core of a vaccine response. The finding could help scientists create more effective vaccines and may lead to potent immune system-based therapies against diseases that have previously eluded vaccines, such as cancer or AIDS.

When the immune system detects an invader, such as a virus, T cells with an affinity for that particular invader multiply rapidly, attack and eliminate infected cells. Once the infection is cleared, however, 90 to 95 percent of those T cells die off, a process called contraction. The five percent or so that survive are known as memory T cells. If a similar infection recurs, these experienced warriors are prepared to rush to the site, recognize that invader and eradicate it again.

Scientists know a great deal about the rapid proliferation and differentiation of these T cells but very little about the factors that regulate contraction. In the September, 2004, issue of Nature Immunology published on-line August 15 -- the researchers show that activation of the gene for the Serine protease inhibitor 2A (Spi2A) can prevent the death of T cells during the contraction phase, resulting in about five times as many memory T cells.

"Drugs based on protective factors such as Spi2A could provide an enormous boost to vaccines," said study author Philip Ashton-Rickardt, professor of pathology and a member of the committee on immunology at the University of Chicago. "This could allow us to extend the duration of an immune response against chronic infections or to focus the power of the immune system on tumor cells, targets that have thus far been quite elusive."

The researchers began by screening approximately 11,000 genes from mouse T cells, to find the small number of genes that were more active in the T cells that survived th
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Contact: John Easton
jeaston@uchospitals.edu
773-702-6241
University of Chicago Medical Center
15-Aug-2004


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