Tolerance and Immunomodulation
For islet transplants to survive long term, we must create an environment that promotes tolerance of transplanted cells without the use of chronic immunosuppression.
- One exciting area of focus is the study of Myeloid Derived Suppressor Cells (MDSCs). Studies have shown that in cancer patients, MDSCs are recruited to the site of the tumor, then inhibit the immune system’s ability to mount an attack against the cancer – essentially protecting the tumor. We want to use these naturally occurring MDSCs for the better - to protect transplanted islets. Dr. Luca Inverardi, Deputy Director, Translational Research at the DRI, will present results of a study showing that MDSC-like cells can be generated from bone marrow as well as umbilical cord blood. In his plenary address to the joint congress, Dr. Inverardi, who is Co-Chair of the Joint Scientific Program Committee for the CTS IXA, will present increasing evidence that MDSCs could represent an important tool for the treatment of autoimmune diseases and to prevent transplant rejection.
- Dr Inverardi will also report on preliminary data that initially suggest the administration of filgrastim, a drug normally used to stimulate expansion of white blood cells, results in better outcomes in islet transplant recipients. Filgrastim has been linked to the expansion of MDSCs.
- In related research, we studied the role of a protein called CCL21. Similar to MDSCs, CCL21 production has been shown to induce local immunosuppression that promotes the induction of protective regulatory T cells. Dr. Alice A. Tomei, junior scientist at the DRI, will present results indicating that CCL21 may show promise in diabetes research by recruiting MDSCs to the site of CCL21-expressing grafts. We want to take advantage of the way tumor cells successfully evade immune recognition and use it to promote acceptance of islet grafts.
- Dr. Antonello Pileggi, Director of Preclinical Cell Processing and Translational Models Program at the DRI, will be delivering two presentations on progress we've made to improve islet engraftment by preventing inflammatory reactions. In the first study, which will be presented by Dr. Carmen Fotino, a postdoctoral fellow and member of Dr. Pileggi’s research team, it is demonstrated that antioxidants can be used to maximize the induction of immune tolerance and acceptance of transplanted islets long term. A second study involved the use of an agent used to inhibit specific signals involved in immune cell activation and responses during inflammation, rejection and autoimmunity. Both studies demonstrate the critical role of targeting inflammation pathways at the time of islet transplantation to enhance islet engraftment and long-term function.