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Joslin researchers identify key molecule in Type 1 diabetes progression

egulatory T-cells co-existed and thrived in these insulitis lesions, and they wondered what kept these lesions respectful.

They looked specifically at a molecule called inducible co-stimulator (or ICOS), which was expressed at an unusually high level on regulatory T cells. Using monoclonal antibodies (man-made versions of natural antibodies, which target individual proteins like guided missiles), the researchers blocked the action of ICOS to see what would happen. Blocking ICOS disrupted the balance between T effector and T regulatory cells, and provoked insulitis to immediately convert to diabetes. The researchers concluded that ICOS plays an important role in keeping insulitis lesions from becoming destructive.

"Understanding the molecular and cellular basis of the immune regulation in the lesion might some day lead to the development of therapies that favor regulatory T-cells and respectful insulitis, preventing the development of full-blown diabetes even after insulitis has developed," Herman explains.

Mathis and Benoist hold the William T. Young Chair in Diabetes at Joslin and co-head the Section on Immunology and Immunogenetics. Both are Professors of Medicine at Harvard Medical School. The research was funded by the National Institutes of Health and the Juvenile Diabetes Research Foundation. Gordon J. Freeman, Ph.D., of the Dana Farber Cancer Institute collaborated on the study.

In type 1 diabetes, which affects an estimated 800,000 Americans, the insulin-producing beta cells of the pancreas have been destroyed. People with type 1 diabetes must take insulin to survive, and are at greater risk for heart attack and stroke, as well as diabetes-related diseases of the eyes, kidneys, and nerves. Currently, type 1 diabetes cannot be cured, but by keeping their blood glucose levels as close to normal as possible, many people with diabetes can prevent or slow down the long-term complications of
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Contact: Marge Dwyer
marjorie.dwyer@joslin.harvard.edu
617-732-2415
Joslin Diabetes Center
23-Jun-2004


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