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: Marcus Pericin, Alana Althage, Stefan Freigang, Hans Hengartner, Eric Rolland, Philippe Dupraz, Bernard Thorens, Patrick Aebischer, Rolf M Zinkernagel
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 99 Issue 12 Pg. 8203-6 (Jun 11 2002) ISSN: 0027-8424 [Print] United States
• PMID: 12060765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Insulin

Topics

• 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