La Jolla researchers create first cellular movies showing destruction underlying type 1 diabetes

April 24, 2017

The Brehm Coalition, a unique type 1 diabetes research collaboration, provided major funding for the two-photon microscope. The Juvenile Diabetes Research Foundation (JDRF) was a significant contributor to the research studies. "Dr. von Herrath was one of a very limited, select group of scientists chosen to receive funding through the JDRF Scholar Award program," said Richard Insel, M.D., the JDRF's chief scientific officer, noting the award targets high-risk, high-reward endeavors. "We are thrilled that Dr. von Herrath's research has provided new insights into the pathogenesis of type 1 diabetes that could lead to novel therapeutic approaches. This is just the kind of pioneering research that the Scholar Award was designed to encourage."Dr. Coppieters said the as-it-happens movies reveal the specific behaviors of various cells. "We're able to see how the beta cells eventually die and how the immune T cells access the pancreas from the blood stream," he said. Among the many insights gained, the researchers were able to identify the specific blood vessels where the T cells (normally none of these reside in the pancreas) enter the pancreas, how the T cells launch an attack and the time sequence of events.

The movies also illuminated particularly interesting information regarding the beta cell destruction process. "The T cells move randomly throughout the pancreas until they encounter the beta cells, where they slow down and release toxic substances that eventually kill the beta cells. What was most surprising is that this 'kiss of death' takes quite a while, elaborate calculations indicated a timeline in the order of hours (to kill a few beta cells)," said Dr. Coppieters.

The scientists also found remarkable the large numbers of T cells needed in the mice - tens of millions -- to produce massive beta cell destruction. "These factors may help to explain the long pre-clinical stage in type 1 diabetes," said Dr. von Herrath, since T cell numbers in the human pancreas are thought to be significantly lower than in mice.

"This means that the autoimmune attack is already ongoing for years before the number of beta cells drops below a critical threshold, resulting in clinical diagnosis," he said, noting that 90 percent of beta cells are destroyed in humans before the disease is usually recognized. "From a therapeutic perspective, these studies suggest that we may need to find a way to prevent the T cells from accessing the pancreas in the first place, since once they do, they have the ability to destroy several beta cells at a time."

Source La Jolla Institute for Allergy & Immunology