A basic science discovery concerning how part of the immune system remembers past opponents may provide the solution to a fundamental problem facing vaccines to treat AIDS or cancer. Researchers from the University of Chicago report in the March 12 issue of the journal Science that the cells that are crucial players for any vaccine against HIV-infected or cancerous cells are distressingly slow learners.

The problem, the researchers demonstrate, is that it takes several generations of intense instruction to make a lasting impression on a T cell. Creating large numbers of "memory" T cells that can recognize a trouble maker they have seen before and attack when they see it again requires prolonged continuous exposure to high levels of the intruder.

"This finding suggests that the typical approach to vaccines for treatment of cancer or AIDS is not often likely to produce the desired result," said author Philip Ashton-Rickardt, Ph.D., assistant professor of pathology at the University of Chicago. "But it also shows us how we can get around the problem."

Ashton-Rickardt's team -- including immunology graduate student Joseph Opferman and post-doctoral fellow Bertram Ober, Ph.D., all from the Gwen Knapp Center for Lupus and Immunology Research at the University of Chicago -- set out to answer a central question in immunology: Where do the T cells responsible for "remembering" a previous infection and fighting it off a second time come from?

When stimulated by an invader, T lymphocytes multiply and attack the infecting foreigner. Once they get the upper hand, most of these T cells are no longer needed and die off. A small percentage, however, survive and stand guard in case this particular invader comes back.

Immunologists have proposed two models of this process. One requires two parallel tracks for cell-killing T lymphocytes. Most of the T cells attack the foreigner then die off soon after victory. But a smaller group of T cells is preprogrammed to
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Contact: John Easton
jeaston@mcis.bsd.uchicago.edu
773-702-6241
University of Chicago Medical Center
12-Mar-1999