application) The recent development of a steroid-free protocol of immunosuppression by Shapiro, et al, based on sirolimus and tacrolimus, has been a major advance in the field of islet transplantation. Insulin independence has been achieved in seven of seven consecutive cases by the University of Alberta group. Intervention was relatively early; none of the patients had chronic renal failure. However, in this series patients were not rendered insulin independent after receiving islets from the first donor pancreas and a second transplant from another donor was required before insulin therapy could be stopped. The primary barrier to successful human islet allotransplantation is cell mediated rejection. However, T cell mediated islet destruction is not the sole mechanism of islet graft injury after transplantation. Non-specific host immune responses involving macrophages and macrophage generated by-products are also detrimental to islet engraftment and function. The addition of an immunosuppressive molecule which is effective in combating these early non-specific host immune responses during the islet engraftment phase would be expected to improve the results of human islet transplantation. 15-deoxyspergualin (DSG) is an immunosuppressive molecule which inhibits many macrophage functions. It has been shown in experimental animal models to enhance early islet allograft function and has been used successfully in human cases of islet/kidney transplantation. The hypothesis to be tested in this research project is that the addition of an induction course of DSG to the immunosuppressive protocol of Shapiro, et al, will result in the achievement of insulin independence after islet transplantation from a single donor pancreas.
