Tolerance Induction Defect in Mice May Lead to Greater Understanding of Type 1 Diabetes in Humans

Date: April 6, 2004

Bar Harbor, Maine - Type 1 diabetes (T1D), formerly called juvenile diabetes, occurs when an abnormal autoimmune response destroys the cells within the body that make insulin. Without insulin-producing cells, a person suffering from T1D usually faces a lifetime of daily insulin injections.

It is well understood that the mistaken destruction of insulin-producing cells in T1D is mediated by T cells, a component of the immune system. However, in a recent paper in The Journal of Immunology, a Jackson Laboratory team led by Dr. David Serreze, in collaboration with The Scripps Research Institute Department of Immunology, found that an important population of T cells contributing to T1D is activated by B cells–another component of the immune system–and then destroys essential insulin-producing cells. A previously unknown mechanism contributing to T1D is that the immune system fails to eliminate this population of B cells.

Immune systems exist to protect a body from invaders such as bacteria and viruses that cause infections. When a body destroys its own cells, the process is categorized as an autoimmune disease, literally “immunity against self.” Every cell in an individual’s body carries molecules that identify it as “self.” The immune system normally does not attack cells with these “self markers.” Scientists say the immune system “tolerates self”–except in an autoimmune disease such at T1D.

A process called tolerance induction normally deletes both T and B cells that have an abnormal capacity to recognize "self" components of the body. It had been previously known that T cell tolerance defects contribute to T1D, but with support from the National Institute of Diabetes and Digestive and Kidney Diseases, a Cancer Center Support Grant, and the Juvenile Diabetes Research Foundation, Dr. Serreze and his team have found that tolerance induction defects in nonobese diabetic mice also result in a failure to delete self reactive B cells.

“The B cells may contribute to T1D in humans in the same way as in the test mice,” said Dr. Serreze. “Because of this, gaining an understanding of the B cell tolerance induction defects in the mice may ultimately aid in developing protocols that might block progression to overt T1D in otherwise susceptible people.”

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Silveira PA, Dombrowsky J, Johnson E, Chapman HD, Nemazee D, Serreze DV. 2004. B Cell Selection Defects Underlie the Development of Diabetogenic APCs in Nonobese Diabetic Mice. The Journal of Immunology 172:5086-5094.

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