Scientists in Japan have found a way to improve on a promising diabetes treatment. In the October 3 issue of The Journal of Experimental Medicine, Masaru Taniguchi and colleagues report that transplanted insulin-producing cells survive better when the activation of a specific type of immune cell is blocked.
Insulin-dependent diabetes is caused by the destruction of the insulin-producing cells in the pancreas (called islet cells) by auto-reactive T cells. The loss of insulin results in an inability to control blood sugar levels. Transplantation of islet cells is an effective way to restore insulin production, but this therapy requires life-long immunosuppression of the patient. Even with immunosuppression, up to half of the transplanted cells are rapidly destroyed by the patient's own T cells.
Taniguchi's group used a mouse model to show that a subset of cells known as natural killer T (NKT) cells instigates the rapid destruction of the islet cells. NKT cells become activated -- likely in response to the stress of the transplant procedure -- and produce an inflammatory molecule called interferon (IFN)-gamma, which helps to activate the auto-reactive T cells. In mice that lack NKT cells or are unable to produce IFN-gamma, the transplanted cells survived.
The group went on to show that multiple doses of a drug (called alpha-galactosylceramide), which activates NKT cells in single doses, caused these cells to produce less IFN-gamma. The decreased IFN-gamma production protected the transplanted islet cells. The authors thus suggest that multiple doses of the same compound, currently in clinical trials in humans, might help prevent the early loss of transplanted islet cells in patients with insulin-dependent diabetes.