Induction of Pancreatic Islet Graft Acceptance: The Role of Antigen Presenting Cells.

Diabetes mellitus is the most common endocrine disease. It is the fourth leading cause of death by disea.se in western countries and it is a worldwide public health problem.H Prolongation of life is achieved by insulin therapy, but an increasing number of diabetic patients are treated for the complications associated with the disease, including blindness and endstage renal failure. Fifty percent of all patients with diabetes develop renal failure in their lifetime.I-5 In patients with Type I diabetes mellitus. insulin production progressively declines and fmally disappears as the beta cells within the islets are destroyed by an autoimmune process which results from a complex interplay between genetic and unknown environmental factors.6-' Replacement therapy with exogenous insulin has prevented acute death but is imperfect and has been ineffective in preventing the chronic complications of the disease. Thus, altemative methods for total endocrine replacement have . been explored, including transplantation of isolated islets as a free graft.s The idea of transplanting pancreatic tissue to reverse diabetes is a century old~IO and recent reviews on the subject are: available.n -15 Procedures for islet isolationl 6-17 have improved significantly during the last decadelll-30 and the use of more powerful immunosuppressive agents such as cyclosporinel6.27.3I" or FK ;0634-36 have resulted in prolonged human islet allograft survival. Insulin independence3I.33-37was obtained in some patients indicating that it is possible to replace the endocrine function of the pancreas by an islet transplant in humans. Despite these encouraging results, rejection remains the major factor limiting clinical trials of islet transplantation in Type I diabetes mellitus.31 .32.3ot-37 The solution to islet rejection cannot be provided by an increase in immunosuppressive protocols, since islet transplantation does not constitute a life-saving procedure. In contrast to other organ transplants such as heart or liver allografts, islet administration to Type I diabetic patients should be considered as prophylaxis to prevent the development of the chronic complications of the disease. Therefore, the risks associated with powerful immunosuppressive treatments cannot be justified at the present time_ In the absence of any major breakthrough in the development of new and more benign immunosuppressive agents, it will be necessary to develop alternative procedures to prevent islet rejection.