GSBS Student Publications

Title

Islet cell autoimmunity and transplantation tolerance: two distinct mechanisms

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Immunology and Virology; Department of Medicine, Diabetes Division; Department of Medicine, Division of Endocrinology and Metabolism

Date

12-18-2003

Document Type

Article

Medical Subject Headings

Animals; *Immune Tolerance; Islets of Langerhans; *Islets of Langerhans Transplantation; Mice; Mice, Inbred NOD

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Recent advances in islet transplantation have enabled physicians to cure type 1 autoimmune diabetes, but at the cost of lifelong immunosuppression with its attendant side effects and long-term health risks. To eliminate the need for immunosuppression, researchers have developed methods for inducing tolerance to transplanted allografts. Tolerance-based transplantation using costimulation blockade has proven remarkably successful in many animal model systems. The most widely used animal model system for studying islet transplantation in type 1-like autoimmune diabetes is the NOD mouse. Unfortunately, this strain has proven resistant to costimulation blockade-based transplantation tolerance protocols that are successful in chemically diabetic mice given islet grafts. It has been assumed that resistance to transplantation tolerance in the NOD mouse is (1) related to autoimmunity directed against its pancreatic beta cells, (2) a consequence of that autoimmunity, and (3) under the control of the same genes that control autoimmunity. In this review, we provide arguments to challenge these assumptions. We describe a new animal model and a new conceptual framework based on data indicating that the mechanisms responsible for resistance to transplantation tolerance and beta cell autoimmunity are not identical. We believe that the recent discoveries we describe will have important implications for the development of tolerance-based transplantation therapies and their translation from the laboratory to the clinic.

Rights and Permissions

Citation: Ann N Y Acad Sci. 2003 Nov;1005:148-56.

Related Resources

Link to article in PubMed

Journal Title

Annals of the New York Academy of Sciences

PubMed ID

14679049