New cellular mechanism represses immune reaction in type I-diabetes

Even though our immune system has evolved to fight invading bacteria and viruses, sometimes the immune tolerance is broken and immune cells attack healthy tissue. In type I diabetes, immune cells kill insulin-producing beta cells in the pancreas. It remains largely unknown how target tissue is damaged by immune cells, what protective mechanisms are in place and how tissue cells respond to inflammatory damage. In the current study, researchers studied this by transplanting insulin-producing pancreatic cells into the mouse eye. The method, developed at Karolinska Institutet, enables researchers to continuously study the cells in detail without damaging the tissue.

This study is the first to show that regulatory T helper cells in the target tissue have long-lasting direct contact with self antigen-directed killer T cells. The finding suggests that protective helper T cells may soften the aggressiveness of tissue-damaging T cells and control the immune reaction.The investigators also found that bystander tissue cells in the vicinity of attacked cells are not killed. Instead, they regenerate the damaged tissue by undergoing replication.

”This study shows that the tissue cells may not be mere 'sitting ducks' in a setting of autoimmune cell destruction. Rather, they may be capable of a resilient response at the inflammatory front,” says Per-Olof Berggren at the Rolf Luft Research Center for Diabetes and Endocrinology at Karolinska Institutet, one of the researchers behind the study.

The results suggest that insulin-producing beta cells can regenerate in the body by replication, resulting in a doubling in cell mass within days.

”The direct visual evidence open a number of exciting new doors for both immune cell and islet beta cell biology/pathology, which will ultimately lead to tissue regenerative therapies in type 1 diabetes and other disorders caused by immune damage,” says Zhibin Chen at the Department of Microbiology and Immunology of the University of Miami Miller School of Medicine, principle investigator of the study.

The study was financially supported by the National Institute of Health, the Diabetes Research Institute Foundation, the Swedish Research Council and the Family Erling-Persson Foundation. Per-Olof Berggren is one of the founders of the company Biocrine, which is going to commercialise the method used in the study.

Publication: 'Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance', Jason Miska, Midhat H. Abdulreda,Priyadharshini Devarajan, Jen Bon Lui, Jun Suzuki, Antonello Pileggi, Per-Olof Berggren, and Zhibin Chen, Journal of Experimental Medicine (JEM)x, online 24 february, doi: 10.1084/jem.20130785, March 2014 paper issue.