Gordon Wilson lecture. The prevention of immune rejection of islet transplants without the use of immunosuppressive drugs.
The findings in this series of investigations indicate that the passenger leukocyte concept applies to islet transplants. Six methods have been developed which prevent rejection of islet allografts in rats and mice without requiring the continuous use of immunosuppressive drugs in the recipient. Initial studies indicate that the passenger leukocyte concept also applies to the prevention of rejection of islet allografts in the dog. Thus the problems remaining with respect to human application are two. One is to determine which of the six methods will completely prevent rejection of islet allografts in dogs and could serve as a model for human application. The second is to modify and adapt the Velcro technique and the automated procedure for mass isolation of islets to the human pancreas. When we have been successful in modifying these isolation procedures so that we can obtain at least 100-150,000 islets, then human islets will be transplanted into the omentum of diabetic subjects who have received a kidney transplant and are already being treated with immunosuppressive agents. The purpose of these initial studies in humans will be to determine whether a sufficient mass of endocrine islet tissue has been transplanted to maintain normoglycemia and normal carbohydrate metabolism in these individuals. We hope that by the time these studies are completed we will have finished the studies in dogs on the selection of the optimal method for preventing rejection and will then be able to initiate human islet transplants without the use of immunosuppressive drugs. Dr. Davie and I also believe that these methods may be applicable to the prevention of rejection of other tissues and organs. It should be quite easy to apply these procedures to transplants of the parathyroid. Dr. Lafferty already has evidence that parathyroid tissue is present in established allografts of thyroid in mice following in vitro culture of the thyroid in 95% O2. It is possible that the procedures will also apply to other endocrine tissue such as the adrenal, the ovary and neuroendocrine tissue. In addition, some of the procedures that have been developed recently could be used for perfusion of organs such as the heart, kidney and liver before transplantation to determine whether alteration or removal of passenger leukocytes in these large organs would affect the survival of the allografts. It is apparent that these past few years have been extremely exciting and we only hope that the next few years will be even more exciting.
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000601:surgery; D004285:Dogs; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014466:Ultraviolet Rays
D000961:Antilymphocyte Serum; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents