title: Allogeneic beta-islet cells correct diabetes and resist immune rejection.
abstract: 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.
authors.affiliation: Institute of Experimental Immunology, Department of Pathology, University of Zürich, 8091 Zürich, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Pericin
authors.forename: Alana
authors.initials: A
authors.lastname: Althage
authors.forename: Stefan
authors.initials: S
authors.lastname: Freigang
authors.forename: Hans
authors.initials: H
authors.lastname: Hengartner
authors.forename: Eric
authors.initials: E
authors.lastname: Rolland
authors.forename: Philippe
authors.initials: P
authors.lastname: Dupraz
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
authors.forename: Patrick
authors.initials: P
authors.lastname: Aebischer
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology / Q000502:physiology*; D007328:Insulin / Q000032:analysis; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D007328:Insulin