Antibody therapy prevents type 1 diabetes in mice

More than 700,000 Americans have type 1 diabetes, an autoimmune disorder in which the body errantly attacks the insulin-producing cells of the pancreas, causing chronically elevated levels of sugar in the blood, leading to blindness, kidney failure, heart disease and nerve damage. Previously known as juvenile diabetes, type 1 diabetes is usually diagnosed at a very early age, but in some cases it can be diagnosed in adulthood.

In this study, the Pitt researchers treated non-obese diabetic (NOD) mice with an antibody — a type of protein produced by the immune system that recognizes and helps fight infections and other foreign substances in the body — directed against a receptor known as CD137 on the surface of a type of immune cell called T-cells. Treating NOD mice with the anti-CD137 antibodies significantly suppressed the development of diabetes, whereas most of the control mice developed diabetes by the time they were six months old.

Interestingly, the antibody therapy did not appear to cure the NOD mice because the researchers were still able to see lymphocytes in their pancreatic islets, a tell-tale sign of pancreatic inflammation and autoimmunity. In addition, when the researchers isolated cells from the spleens of the antibody-treated mice and injected these cells into immune-deficient NOD mice, seven of the nine recipient mice developed type 1 diabetes, indicating that the donor mice still harbored pathogenic T-cells. On the other hand, when the researchers transferred a certain subset of T-cells from anti-CD137-treated mice that expressed two other receptors known as CD4 and CD25 to other immune-deficient NOD mice, it prevented the onset of diabetes in the recipient mice.

According to senior author William M. Ridgway, M.D., assistant professor in the University of Pittsburgh School of Medicine's department of rheumatology and clinical immunology, this therapy, if given early enough, may offer a viable method for preventing the onset of type 1 diabetes in genetically at-risk people.

“Our studies and others suggest that CD137 plays a significant role in the development of and genetic predisposition to type 1 diabetes. In this study, for the first time, we have demonstrated that CD137 antibody therapy can suppress the development of type 1 diabetes in mice and that the effect is dependent on the induction of a certain subset of regulatory T-cells. If we can demonstrate this same genetic predisposition and therapeutic effect in human type 1 diabetes patients, then this may prove to be a significant step toward preventing this disease before it can take hold,” he explained.