Immune cell entry into the pancreatic islets key to understanding type 1 diabetes origins

St. Jude Children's Research Hospital investigators have discovered how destructive immune cells gain access to insulin-producing cells and help cause diabetes.

The finding points to possible new strategies to halt or prevent type I diabetes.

Working in mice, researchers demonstrated that to enter key areas of the pancreas known as the islets of Langerhans, immune cells known as T cells must recognize a marker on the surface of insulin-producing cells housed there. T cells play a key role in regulating immune response. Once inside the islets, T cells trigger the inflammation that can lead to destruction of the insulin-producing beta cells. The result is type I diabetes.

The report answers a fundamental question about the role of T cell entry and accumulation in the islets in development of type I disease, a disease that affects as many as 3 million Americans. The research appears in the October 16 edition of the journal Immunity. Dario Vignali, Ph.D., is the paper's senior author and vice chair of the St. Jude Immunology department.

The St. Jude results contradict a widely held theory that only a small percentage of T cells that infiltrate the islets were actively involved in causing type I diabetes. The old scenario held that most of the T cells found in the islets were recruited to the site by a small number of specialized T cells. Those recruited or bystander T cells were thought to play no role in causing diabetes. Furthermore, it was thought that any T cell could gain access to the islets.

"The new research argues that every T cell in the islet is important. What these T cells recognize that allowed them to gain access to the islets may provide us with clues as to what might be needed to prevent diabetes," Vignali said. "Understanding the molecular differences between the T cells in the islets and the T cells in the periphery might also start to tell us a lot about what it takes to make a T cell attack the beta cells and cause diabetes."

Without insulin to turn food into fuel for cells, patients develop type I diabetes and are left dependent on insulin injections, an insulin pump or in rare cases a pancreas transplant. Unlike the more common form of the disease, known as type II diabetes, type I diabetes usually affects children and is sometimes called juvenile diabetes. About 15,000 new cases are diagnosed annually in the United States. Even with treatment, patients with type I diabetes are at risk for blindness, kidney failure and other complications.

"This paper also presents a new clinical intervention strategy—blocking T cells from even getting into the islet cells in the first place," Vignali added.

If any T cell could enter the islets, then it would be less likely that there were any "special rules" for entering islets and thus nothing unique about entry into the islets that might be targeted by treatment, he explained.