The Kent and Harlan Labs Isolated Immune Cells from Islets of Donors with Type 1 Diabetes
Date Posted: Monday, October 31, 2016
In a highly collaborative effort, scientists at the UMass Diabetes Center of Excellence isolated and characterized a large bank of live islet-infiltrating T cells directly from the islets of tissue donors with type 1 diabetes. The findings, published in Nature Medicine, have direct implications for the design of therapies and preventative strategies for people with type 1 diabetes and those at risk for developing it.
In autoimmune diseases, a major goal of the design of preventative strategies & therapies is the ability to turn off the immune system’s destructive responses to specific tissues (self- or autoreactivity) while leaving the rest of the immune system intact to respond to challenges, such as infections. In type 1 diabetes, lymphocytes infiltrate and destroy the insulin-containing cells in the pancreatic islets of Langerhans, leading to diabetes.
“This is a major advance in our ability to understand this destructive autoimmune process, directly from human islets,” said David M. Harlan, MD, the William and Doris Krupp Professor of Medicine, co-director of the UMass Diabetes Center of Excellence and a co-author on the paper. “Our ability to probe the function of these cells in the past has been limited. Now, we are able to derive, right from the source of injury in type 1 diabetes, the live T cells responsible for this pathology.”
Using live islets from nine type 1 diabetic donors, the largest cohort studied thus far, Sally C. Kent, PhD and postdoctoral fellow Jenny Aurielle B. Babon, PhD, sorted live lymphocytes from the islets by fluorescence activated cell sorting (FACS). They also used an improved tissue culture method they developed to grow lymphocytes from the islets. Overall, Dr. Kent derived 236 T cell lines from the islets and analyzed the function of 50 lines, discovering the specific reactivities of 18 lines. From previous studies, it's known that T cells react to some previously known antigens (targets of the T cells) as well as to newly discovered modified antigens with alterations called post-translational modifications.
“We found T cells from the islets that recognized the previously identified antigens as well as T cells that recognized post-translationally modified antigens," said Dr. Kent. "This was a surprise. There's a much broader repertoire of islet-infiltrating T cells than we previously thought. This information, and the information we will continue to discover from this bank of T cells, opens the door for the design of durable immunotherapies for type 1 diabetes.”
The research was the result of a collaborative effort by investigators from around the world. Significant contributions were made by scientists at the Network of Pancreatic Organ Donor with Diabetes (nPOD), JDRF, Vanderbilt University and other institutions and organizations.