Scientists have come a step closer to understanding the cause of childhood diabetes, a disease in which the immune system body destroys its own insulin-producing cells. A paper in the September issue of Nature Medicine suggests that the insulin itself, on the surface of cells that produce it, triggers destruction. The study may help develop strategies to prevent the disease
Previous studies had shown that T cells, immune cells that normally fight infection, are responsible for the attack. - And destroy - the so-called island b cells, insulin factories in the pancreas. The attack can rob patients of the ability to produce insulin for the rest of their lives. Many scientists are trying to identify this protein in b cells is the antigen that triggers the attack, hoping that it can be used in some way to "teach" the immune system that n is not an enemy.
Much of the research involved the CD4 or "helper" T cells, which interact with other immune cells to trigger the production of antibodies and other immune responses, contributing to the development of diabetes. But immunologists Susan Wong, Charles Janeway and colleagues from Yale University were more interested in another class of T cells, called CD8 cells or killer T. In 1996, they isolated an aggressive CD8 cells from mice with a disease very similar to human diabetes and showed that, when transplanted into other mice, it causes diabetes in less than a week. Because cells from young mice that are not sick yet, but later developed diabetes, the researchers thought that the cells could play a role in the first phase of the disease, maybe even start the immune attack on islet cells.
In the current study, the team set out to find that the CD8 cells could recognize the islet cells. First, they took the tumor cells multiply rapidly and genetically engineered to produce them en masse hundreds of pancreatic proteins. Then, they inserted a gene in their CD8 T cells that causes the cells turn blue when they cling to the particular antigen which activates them. In this way they were able to identify insulin as the antigen; they may even identify a specific sequence of nine amino acids of the hormone that T cells recognized.
Wong said it is the first time researchers have identified a trigger for the CD8 cells in autoimmune disease. "It is a beautiful study," agrees immunologist George Eisenbarth of Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver. "This new insight into the role of insulin is exciting."
In addition, Wong said, the conclusion that insulin is the likely culprit bolsters the rationale for an idea that is already being tested. For reasons not well understood, some trigger disease antigens, when taken orally, can suppress immune reactions that would otherwise be directed against them, and clinical trials are underway to see if the oral insulin can inhibit the development of diabetes in children at risk of disease. The results suggest another possibility as well, Eisenbarth said. If insulin reactive CD8 cells are the source of the disease, researchers may be able to find ways to disarm.
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