St JudeResearchers from St. Jude Children’s Research Hospital claim to have found how disparaging immune cells could get access to insulin-producing cells and aid in causing diabetes.

Working on mice, the researchers verified that to penetrate in important regions of the pancreas called the islets of Langerhans, immune cells known as T cells ought to identify a marker on the surface of insulin-producing cells housed there. T cells may play a vital function in adapting immune response. Once inside the islets, T cells could activate the inflammation that may result in the damage of the insulin-producing beta cells. The outcome is type I diabetes.

The St. Jude results challenge a generally held hypothesis that apparently only a tiny percentage of T cells that penetrate the islets were actively occupied in causing type I diabetes. The old scenario held that the majority of the T cells in the islets were supposedly enlisted to the location by a small amount of specialized T cells. Those enrolled or bystander T cells were thought to play no part in causing diabetes. Also, it was believed that any T cell could get entry to the islets.

Dario Vignali, Ph.D, is the paper’s senior author and vice chair of the St. Jude Immunology department, commented, “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. 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.”

About 15,000 new cases of type I diabetes are detected yearly in the United States. Patients with type I diabetes are at a threat for blindness, kidney failure and other complications, even with treatment.

For this research, scientists used a method that Vignali’s laboratory created in 2006. The technique lets researchers swiftly adapt to T cell production in mice. Usually mice make millions of T cells that could identify many diverse cells and microorganisms. Every T cell carries a receptor on its surface that identifies and attaches to just one particular antigen, or marker, on the surface of the T cell’s anticipated target.

The alteration method let researchers to form strains of mice with only two kinds of T cells, each with different receptors. One set apparently carried a receptor that identified the insulin-producing beta cells and could cause diabetes. The other group was supposedly programmed to know a different antigen. Researchers accounted they could not provoke the latter group of T cells to penetrate the islets.

Then researchers formed and trailed T cells with three kind of receptors. The first kind is the receptor from T cells with an established aptitude to go through islet cells and cause diabetes. The second kind is the one that could enter islets and cause inflammation, but not diabetes. The third group of receptors is the one with supposedly no link to type 1 diabetes or islet cells. The scientists accounted that none of the T cells, even those with an established capability to cause diabetes in mice, could provoke bystander T cells to penetrate the islet cells.

Ultimately, researchers tracked T cells transporting receptors from mice that may usually develop type I diabetes. They created mice with about 17 new T cell receptors, around five from the spleen of diabetic mice and roughly 12 from T cells secluded in the islets of those diabetic mice. If the islets regulate T cells entry, then islets in the new mouse strains could be penetrated by T cells with islet-derived, but not spleen-derived, receptors.

Viagnali mentioned, “About 70 percent of the receptors that came from the islets could mediate T cell migration back into the islets, while none of the receptors that came from the spleen could do likewise.”

The islet-derived receptors were also connected to swift development of diabetes, with around one-third causing diabetes during the 10-week research. Vignali mentioned that it is uncertain if the findings will hold true for other autoimmune diseases like rheumatoid arthritis or Crohn’s disease.

The research appears in the Journal Immunity.