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. 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 Zhibin Chen, Ph.D., associate professor of microbiology 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 [a transplantable “mini-organ” developed by Miller’s Diabetes Research Institute that mimics the native pancreas], which will minimize the need for systemic therapies that have harmful side effects,” said Midhat Abdulreda, Ph.D., assistant professor of surgery and also a principal investigator and co-lead author on the study.
The study’s co-authors also include Per-Olof Berggren, Ph.D., from the Karolinska Institutet, who developed the Living Window approach and serves as the DRI’s head of Cell Biology and Signal Transduction and the Mary Lou Held Visiting Scieentist; Dr. Antonello Pileggi, the DRI’s director of Preclinical Cell Processing and Translational Models; Jason Miska, a former Miller School graduate student, who also spearheaded the study, and current Miller School graduate students Priyadharshini Devarajan and Jen Bon Lui, among others.
University of Miami,