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Why good cells go bad in progression of MS

Scientists have pinpointed a chemical messenger that frees some white blood cells from the body's normal constraints, allowing the cells to act like renegades that could damage nerves in the central nervous system. The work, to be published in the July 15 issue of the Journal of Immunology and just published on-line, helps explain one of the fundamental mysteries of multiple sclerosis (MS).

The scientists discovered that a chemical messenger found at high levels in MS patients allows some immune cells known as T- effector cells to evade normal regulation. Instead, the cells bypass their usual gatekeepers and could become active in the body's tissues, including the brain and spinal cord. Scientists believe that during MS, renegade T-effector cells damage the myelin coating that covers nerve cells, causing the disease's symptoms. While another subset of white blood cells called T-regulatory cells normally control the activation of T-effector cells, investigators found that the chemical messenger interleukin-12 or IL12 allows some cells to sidestep that regulation and run amok.

"Normally effector T cells are under strict control as they circulate through the blood stream in order to prevent unnecessary inflammation that could be harmful to otherwise healthy tissues," says Benjamin Segal, M.D., the neurologist who led the University of Rochester study. "However, occasionally they escape the body's suppression system. We're learning how they do that."

In the 1990s, while working in the laboratory of Ethan Shevach, M.D., at the National Institute of Allergy and Infectious Diseases, Segal was one of the first scientists to show that IL12 could be important in autoimmune diseases like MS. He showed that the molecule empowers CD4+ T cells to enter the central nervous system, where they don't belong, and attack myelin. He has also shown that mice without the IL12 gene are completely protected against an MS-like disease, and that ordinary mice can be pr
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Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
11-Jul-2005


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