Mechanism for Generating Autoimmunity-Suppressing Cells Identified

Mechanism for Generating Autoimmunity-Suppressing Cells Identified

March 27, 2001

(PHILADELPHIA — March 28, 2001) Autoimmune disorders, such as lupus, arthritis, and diabetes, are understood to result from immune cells attacking the body's own cells instead of infectious agents such as viruses and bacteria. In a new study, scientists at The Wistar Institute have identified for the first time the mechanism by which the immune system generates regulatory T cells, a specialized type of immune cell that plays a critical role in preventing autoimmunity.

The findings suggest that regulatory T cells are finely tuned toward the recognition of the body's own proteins-or "self"-and that a failure to make a complete repertoire of regulatory T cells may be an important factor in the development of autoimmune disease. In addition, the study suggests that engineering different types of regulatory T cells in the laboratory could one day become a strategy for combating autoimmune diseases.

The research is published in the April issue of Nature Immunology. "We and others showed previously that regulatory T cells suppress autoimmunity, but it was unknown how these cells were generated," says Andrew J. Caton, Ph.D., associate professor at The Wistar Institute and senior author on the study. "Now, we believe we have good insight into that process."

Caton says the prevailing belief has been that the developing T cells most highly reactive to and specific for self proteins are eliminated by the body, and that developing T cells that are somewhat less specifically reactive to self are recruited for the regulatory function. "Our findings contradict that notion and suggest that regulatory T cells recognize self proteins by a highly specific process," he says.

Research published last year by the same laboratory reported that as many as 10 percent of T cells in a normal animal are regulatory T cells, indicating their importance as a safeguard against autoimmunity.

"What's interesting about these regulatory T cells is that, although their purpose is to prevent autoimmunity, they themselves react against self," Caton says. "However, their properties have been changed so that instead of responding to stimulation by dividing and directing the elimination of infected cells, as a normal T cell does, they instead suppress the local immune response."

In the future, Caton and his research team intend to explore how the function of regulatory T cells is disrupted in autoimmunity. In addition, the researchers are interested in determining whether infection by a virus could, under certain circumstances, convert the regulatory T cells into a highly self-reactive but pathological form.

Lead author on the paper is Martha S. Jordan, Ph.D. Other Wistar co-authors are Alina Boesteanu, Ph.D., Amy J. Reed, B.S., Andria L. Petrone, B.S., Andrea E. Holenbeck, B.S., and Melissa A. Lerman, B.A. An additional co-author is Ali Naji, M.D., Ph.D., of the University of Pennsylvania. Funding for the research was provided by the National Institutes of Health.

The Wistar Institute is an independent nonprofit biomedical research institution dedicated to discovering the basic mechanisms underlying major diseases, including cancer and AIDS, and to developing fundamentally new strategies to prevent or treat them. The Institute is a National Cancer Institute-designated Cancer Center- one of the nation's first, funded continuously since 1968, and one of only 10 focused on basic research. Founded in 1892, Wistar was the first institution of its kind devoted to medical research and training in the nation. News releases from The Wistar Institute are available to reporters by direct e-mail or fax upon request. They are also posted electronically to Wistar's home page (http://www.wistar.upenn.edu), to EurekAlert! (http://www.eurekalert.org), an Internet resource sponsored by the American Association for the Advancement of Science, and to the public interest newswire AScribe (http://www.ascribe.org).

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