Islet overexpression of M3 protein by a lentiviral vector prolongs islet graft survival in autoimmune diabetic NOD mice

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The infiltration of autoreactive lymphocytes leads to the destruction of insulin-producing β cells in the islet of the pancreas and induces the Type 1 diabetes mellitus. Non-obesediabetic mice has been served as an animal model for this autoimmune disease due to the spontaneously development of autoimmune diabetes which resembles to human type 1 diabetes. Clinically, islet transplantation has been established as a potential therapy for type 1 diabetes. However, islet grafts in diabetic patients undergo immune destruction results from autoimmune recurrence and allograft rejection. Therefore, it is important to develop an novelstrategy to modulate these two immune responses for treatment of type 1 diabetes. Recent studies have demonstrated that the infiltration of immune cells into islet grafts leads to thedestruction of transplanted islets and dependent on the attraction of immune cells by chemokines. M3 is a 44-kd protein secreted from the cells which wewe infected by murine γ-herpesvirus 68 (MHV-68). M3 protein is a broad range chemokine scavenger that binds to C, CC, CXC, and CX3C chemokines and blocks the activity of these chemokines. The blockade of chemokine activity can inhibit the recruitment of immune cells to the infected site and render the reduction of immune attack. The purpose of this project is to evaluate if the transplanted islets overexpress M3 protein can prolong the protective effect of transplanted islet on type 1 diabetes animal model.