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Experimental Multiple Sclerosis Treatment Targets T Cells

Multiple sclerosis (MS) is one of those mysterious diseases in which the body attacks itself. In this case, immune cells called T cells mistakenly attack the so-called myelin sheaths that protect the signal-carrying fibers of nerve cells, leading to paralysis. But the promising results of an experimental therapy may offer new hope to MS patients and others who suffer from autoimmune diseases. According to a report that will appear in the February issue of the Journal of Immunology, the treatment effectively combated a disease similar to MS in monkeys and could soon be tested in humans.

The new treatment arose from a surprising discovery concerning the T cell trigger. Michael Lenardo of the National Institute of Allergy and Infectious Disease and his colleagues found that whereas T cells exposed to small amounts of myelin sheath protein prompted an immune attack, those exposed to large amounts of the antigen self-destructed. The team thus concluded that introducing large quantities of myelin proteins into the body should dispose of the trouble-making T-cells and arrest the disease. "The therapy is counterintuitive; one might think it would be like pouring gasoline on a fire," Lenardo remarks. Yet the self-destruct feature exists in order to control the number of active T cells, too many of which can be toxic. "In this case, adding more antigen smothers the fire," Lenardo asserts.

In order to test their idea, the team first injected nine monkeys with enough myelin protein to stimulate a T cell attack against their myelin sheaths, inducing an MS-like disease. They then divided the monkeys into three groups. Monkeys in the first group received large doses of myelin protein, monkeys in the second group received moderate amounts, and those in the third group received nothing. After 105 days of observation, monkeys in the third group all exhibited symptoms of the disease. None of the monkeys in the first group, in contrast, showed symptoms, and monkeys in the second group showed significantly delayed symptoms. Magnetic resonance imaging of their brains did reveal damage in those monkeys that had received the high dose, but it was relatively minor.

Moreover, unlike current treatments for MS, which broadly suppress the immune system, the T cell-targeted experimental therapy did not appear to cause adverse side effects. Whether or not the the new treatment will be effective in humans remains to be seen. For now, the team is now studying how it works against other autoimmune diseases in mice.

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