Researchers at Joslin Diabetes Center, Harvard Medical School, and other institutions have identified the function of a protein, dubbed aire, that is critical to helping immune cells learn to recognize--and avoid attacking--the far-flung organs and tissues of the body. The protein appears to work by turning on in the thymus, which lies beneath the breast bone, the production of a wide array of proteins from the body's periphery. The discovery could shed light not only on how the healthy immune system develops tolerance to its own proteins but also how tolerance is lost, as it is in diabetes, rheumatoid arthritis, Crohn's disease and other autoimmune illnesses.

"Our findings lead back to humans because they tell us about a very important mechanism for controlling autoimmunity," said Diane Mathis, a Harvard Medical School professor of medicine at Joslin. "At the same time, they may help us understand why people develop autoimmune diseases." The findings are reported in the Oct. 11 Science.

Until recently, immune cells, in particular T cells, were thought to learn their most basic lesson--attack foreign proteins but spare those that are native--in one of two places. Those with a broad mandate, namely to monitor widely expressed cellular proteins or proteins circulating in the bloodstream, were thought to be trained to distinguish self from foreign proteins while still in the thymus. Cells that recognize proteins in organs and tissues in the periphery, such as the pancreas, thyroid, and adrenals, were believed to learn the self-vs.-nonself lesson once they left the thymus. This organ was thought incapable of producing proteins made by distant organs such as the liver, brain, and pancreas.

But it appears that T cells in training may be learning the lesson while still in the thymus. Building on work of other groups, first author Mark Anderson, a research fellow in medicine at Joslin; Emily Venanzi, a Harvard Medical School graduate student in im
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Contact: Marge Dwyer
Marjorie.Dwyer@joslin.harvard.edu
617-732-2415
Harvard Medical School
10-Oct-2002

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