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Small subset of cells has big role in controlling immunity, study finds

A small subset of cells that tells the immune system whether to attack may be a future target for therapies to help patients fight tumors and keep transplanted organs, a Medical College of Georgia researcher says.

Dendritic cells roam the body, picking up invaders, such as a virus or cancer, then show their finds to the T-cells and tell them how to respond, says Dr. Andrew L. Mellor, molecular geneticist and immunologist and director of the MCG Immunotherapy Center.

Work published in the Aug. 15 issue of The Journal of Immunology by Dr. Mellor and his colleagues gives further clues over what direction dendritic cells will give.

They have shown that giving mice an experimental immunosuppressive agent causes a select number of these cells to express an enzyme, indoleamine 2,3 dioxygenase, or IDO, and that those cells tell T-cells not to respond.

"They are a very fascinating new subset of dendritic cells previously not recognized," says Dr. Mellor, Georgia Research Alliance Eminent Scholar in Molecular Immunogenetics. "We do not think all dendritic cells have the capacity to express IDO. The magic of this subset is their ability to do that," he said of the enzyme first identified for its role in helping a fetus escape rejection by the mother's immune system.

"One of the things we argue in this paper is that we can use IDO to help us find out if dendritic cells are going to stimulate the immune system or turn it off. If they express IDO, they will not stimulate T cells to respond. If they don't express IDO, they are likely to stimulate immune responses once they mature," Dr. Mellor says.

Five years ago nearly to the day, Dr. Mellor and his colleagues, Drs. David Munn and Simon Conway, were reporting in the journal Science that the developing fetus uses IDO to locally disable the mother's immune system. It works by degrading tryptophan, an amino acid critical to the survival of T-cells, which get their action cues from d
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Contact: Toni Baker
tbaker@mail.mcg.edu
706-721-4421
Medical College of Georgia
15-Aug-2003


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