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Diabetes Researchers Shed New Light on Immune Tolerance and Beta Cell Regeneration 

Islet graft before growth viewed through Living Window
 
Islet graft after growth viewed through Living Window
An islet graft before (top) and after growth (blue) at the interface with the destroyed islet (gray). The videos (click each image to view animation) show islet regeneration by adult beta cell replication, one of the striking findings of the study. This demonstrates the resilient response of the bystander islets in the face of immune attack at adjacent islets by damaging T cells (green).

Miami, FL - February 27, 2014 -- Scientists at the Diabetes Research Institute (DRI) and the University of Miami Miller School of Medicine together with their collaborators at Sweden’s Karolinska Institutet have uncovered new mechanisms of the immune system that may help protect the insulin-producing beta cells that are destroyed in patients with type 1 diabetes. In the study, which was published online in the February 24 issue of The Journal of Experimental Medicine, the researchers were able to observe the interactions between specific populations of immune cells involved in beta cell destruction and how these signals may even cause the damaged cells to regenerate. 

In type 1 diabetes, an autoimmune disease, the patient’s immune system mistakenly attacks the insulin-producing beta cells within the islets of Langerhans of the pancreas. However, it remains unknown as to how these cells are damaged by the immune system, what protective mechanisms are in place, and how the targeted cells respond to an attack, if at all.

In the study, conducted in experimental models, the researchers were able to observe these cell-to-cell interactions in vivo using the “Living Window,” a novel approach to viewing transplanted islet cells in real time within the anterior chamber of the eye. Particularly, two key findings of this study may open new doors for further progress in immune tolerance and beta cell regeneration.

First, immune tolerance is facilitated by contact-based interactions among different types of immune cells, including regulatory T cells, pathogenic T cells and dendritic cells. This study demonstrates for the first time that there are long-lasting interactions between regulatory T cells and pathogenic T cells, suggesting that the effects of tissue-damaging T cells may be hampered locally by the protective regulatory T cells in the target tissue.

Second, contrary to prevailing thought, bystander cells are not killed by immune cells but rather replicate in numbers to replace the damaged tissue. The study demonstrates that the targeted cells may not be “sitting ducks,” but instead may respond with resilience when attacked. The researchers observed dramatic growth of the beta cells, even a doubling of mass, within days in the absence of any pharmacological stimulation (to induce the growth of the cells).

“We observed the natural interactions between the various subsets of immune cells and target tissue cells,” said Dr. Zhibin Chen, associate professor of microbiology at UM’s Miller School of Medicine and one of the study’s principal investigators. “The direct visual evidence opens a number of exciting new doors that may ultimately lead to regenerative tissue therapies in diabetes and other autoimmune disorders.”

“These findings may help lead to developing localized targeting of immune mechanisms exclusively in the transplanted tissue, such as pancreatic islets within a DRI BioHub, which will minimize the need for systemic therapies that have harmful side effects,” said the DRI’s Dr. Midhat Abdulreda, assistant professor of surgery and also a principal investigator and co-lead author on the study.

The study’s co-authors also include Dr. Per-Olof Berggren from the Karolinska Institutet, who developed the Living Window approach and serves as the DRI’s head of Cell Biology and Signal Tranduction and the Mary Lou Held Visiting Scientist; Dr. Antonello Pileggi, DRI director of Preclinical Cell Processing and Translational Models; Jason Miska, a former graduate student at the University of Miami, who also spearheaded the study, and UM graduate students Priyadharshini Devarajan and Jen Bon Lui, among others.

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