Taking aim at culprit cells in diabetes

Date: April 23, 2008

Bar Harbor, Maine -- Insulin injections help to keep type 1 diabetes patients alive, but many patients still suffer the worst effects of the disease, from tissue damage to organ failure and early death. So, finding ways to prevent diabetes in the first place is a high priority.

Scientists at Albert Einstein College of Medicine of Yeshiva University in Bronx, N.Y., and Rockefeller University in New York, N.Y., in collaboration with Drs. David Serreze and Yi-Guang Chen of The Jackson Laboratory, have now shown that it's possible to destroy a certain kind of cell that is implicated in the cascade of cellular mechanisms that lead to diabetes. This research is "a proof of concept," Dr. Serreze said, that theoretically could be the foundation of a new strategy to prevent diabetes.

In healthy people, T cells are part of the body's homeland security team. Viruses and bacteria may sneak into the body, but T cells catch many of them by sniffing out certain proteins that are found in those invading agents. But in diabetes, some rogue T cells attack proteins in insulin-producing beta cells in the pancreas, necessitating those insulin injections. 

Several years ago the laboratory of Jackson Professor David Serreze, Ph.D., identified a specific kind of these misguided, autoreactive T cells, called AI4. "Then we developed a mouse model that had only the AI4 kind of T cells," he said. "This was a valuable model for understanding how AI4 cells alone can cause diabetes."

T cells don't function until they've received their marching orders from another kind of cell. Antigen-presenting cells teach T cells which kinds of protein to target. "My collaborators made a very interesting observation," Dr. Serreze said. "They found that the way a protein is introduced to the antigen-presenting cell determines whether or not AI4 autoreactive T cells are activated."

In research published online on April 21 in the Proceedings of the National Academy of Sciences, Dr. Serreze's Albert Einstein and Rockefeller colleagues showed that it's possible to destroy AI4 cells.

"This approach shows you can cause one particular kind of autoreactive T cells -- the AI4s -- to die," Dr. Serreze said. "Are other kinds also implicated in diabetes, and if so, how many of them can we kill off? The next step will be to see whether we can use this method to actually prevent diabetes in the mouse model."

Dr. Serreze noted, "There's a lot of development to go before this can begin to be translated into treatment for people. But it at least provides an insight into a way we might be able to prevent diabetes in people who are genetically at high risk for the disease."

The Jackson Laboratory is a nonprofit biomedical research institution and National Cancer Institute-designated Cancer Center based in Bar Harbor, Maine. Its mission is to discover the genetic basis for preventing, treating and curing human diseases, and to enable research and education for the global biomedical community.

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Proceedings of the National Academy of Science: Selective delivery of β cell antigen to dendritic cells in vivo leads to deletion and tolerance of autoreactive CD8+ T cells in NOD mice: Arunika Mukhopadhaya, Tadashi Hanafusa, Irene Jarchum, Teresa P. DiLorenzo, Albert Einstein College of Medicine; Yi-Guang Chen, David V. Serreze, The Jackson Laboratory; Yoshiko Iwai, Ralph M. Steinman, Kristin V. Tarbell, The Rockefeller University.

Contact(s): Joyce Peterson, joyce.peterson@jax.org, 207-288-6058

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