Allogeneic beta-islet cells correct diabetes and resist immune rejection
Allogeneic MHC-incompatible organ or cell grafts are usually promptly rejected by immunocompetent hosts. Here we tested allogeneic beta-islet cell graft acceptance by immune or naive C57BL/6 mice rendered diabetic with streptozotocin (STZ). Fully MHC-mismatched insulin-producing growth-regulated beta-islet cells were transplanted under the kidney capsule or s.c. Although previously or simultaneously primed mice rejected grafts, STZ-treated diabetic mice accepted islet cell grafts, and hyperglycemia was corrected within 2-4 weeks in absence of conventional immunosuppression. Allogeneic grafts that controlled hyperglycemia expressed MHC antigens, were not rejected for >100 days, and resisted a challenge by allogeneic skin grafts or multiple injections of allogeneic cells. Importantly, the skin grafts were rejected in a primary fashion by the grafted and corrected host, indicating neither tolerization nor priming. Such strictly extralymphatic cell grafts that are immunologically largely ignored should be applicable clinically.
Keywords: Animals ; Blood Glucose/metabolism ; Diabetes Mellitus ; Experimental/*surgery ; Graft Rejection/*prevention & control ; Graft Survival/immunology/*physiology ; Insulin/analysis ; Islets of Langerhans Transplantation/*immunology/pathology ; Major Histocompatibility Complex ; Mice ; Mice ; Inbred C3H ; Mice ; Inbred C57BL ; Skin Transplantation/*immunology ; Time Factors ; Transplantation ; Homologous ; Mice ; Mice
Institute of Experimental Immunology, Department of Pathology, University of Zurich, 8091 Zurich, Switzerland.
Record created on 2008-08-27, modified on 2016-08-08