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Penn study demonstrates new way to boost immune memory
Date:6/4/2009

PHILADELPHIA - After a vaccination or an infection, the human immune system remembers to keep protecting against invaders it has already encountered, with the aid of specialized B-cells and T-cells. Immunological memory has long been the subject of intense study, but the underlying cellular mechanisms regulating the generation and persistence of long-lived memory T cells remain largely undefined. Now, University of Pennsylvania School of Medicine researchers have found that a common anti-diabetic drug might enhance the effectiveness of vaccines. The findings are described this week in an advanced online publication of Nature.

In this study, an experimental preventive vaccine was made more efficacious by boosting numbers of cancer fighting T cells with the anti-diabetic drug metformin. This resulted in a larger population of memory immune cells that were able to fight off a tumor at a later time.

"We serendipitously discovered that the metabolizing, or burning, of fatty acids by T cells following the peak of infection is critical to establishing memory in those T cells," says senior author Yongwon Choi, PhD, Professor of Pathology and Laboratory Medicine. "As a consequence, we used the widely prescribed anti-diabetic drug metformin, which is known to operate on fatty-acid metabolism, to enhance this process."

"We have shown experimentally in mice that metformin increases T-cell memory as well as the ensuing protective immunity of an experimental anti-cancer vaccine," notes postdoctoral fellow and first author Erika Pearce, PhD.

"These findings were unanticipated, but are potentially extremely important and could revolutionize current strategies for both therapeutic and prophylactic vaccines," says Choi.

The lab developed mice deficient in TRAF6, a protein important in the immune response. They found that CD8 T cells deficient in TRAF6 mount an initial response, meaning they are able to proliferate into an ar
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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