Small subset of cells has big role in controlling immunity, s...( endritic cells. The MCG scienti...)

The MCG scientists have focused many of their efforts since on how to use the IDO mechanism to manipulate the immune system to the patient's advantage. In the case of transplant patients, they want the immune system to ignore the new organ; in the case of autoimmune diseases such as type 1 diabetes, they want it to stop a self-destructive attack on pancreas cells that produce insulin. Conversely, they want to prompt the immune system to destroy persistent tumors. In fact, their subsequent studies have shown some tumors express IDO, apparently much as the fetus, which may help them escape the immune response. Persistent infections such as HIV, the virus that causes AIDS, may also rely on the IDO mechanism to avoid destruction by the patients' immune system.

A second Science paper by Drs. Munn and Mellor in September 2002 reported that human dendritic cells could express IDO and showed how the expression suppressed the proliferation of T-cells. "The idea of it simply being expressed in the dendritic cells completely alters our understanding of how dendritic cells talk to T-cells," Dr. Mellor says. "What is it that makes a dendritic cell decide to express IDO or not, that is the key question."

Now in animal studies they have made a select number of dendritic cells do just that by giving the drug CTLA4-Ig, a reagent designed to block the action of T-cells. The reagent is still in clinical trials to evaluate its potential for patients with transplants and autoimmune diseases such as multiple sclerosis. In November, scientists from the University of Perugia in Italy were the first to report that treatment with CTLA4-Ig induced the IDO mechanism in dendritic cells, a move that ultimately keeps T-cells from responding.

Although dendritic cells were believed to be a fairly homogenous group, the MCG scientists have shown that only a small number of the cells respond to the reagent. They also used the IDO knockout mice develop
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Contact: Toni Baker
tbaker@mail.mcg.edu
706-721-4421
Medical College of Georgia
15-Aug-2003