GSBS Student Publications

Title

Islet allograft survival induced by costimulation blockade in NOD mice is controlled by allelic variants of Idd3

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

7-28-2004

Document Type

Article

Medical Subject Headings

Alleles; Animals; CD40 Ligand; Combined Modality Therapy; Diabetes Mellitus, Type 1; Graft Survival; Immunotherapy; Islets of Langerhans Transplantation; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Transplantation, Homologous; Variation (Genetics)

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

NOD mice develop type 1 autoimmune diabetes and exhibit genetically dominant resistance to transplantation tolerance induction. These two phenotypes are genetically separable. Costimulation blockade fails to prolong skin allograft survival in (NOD x C57BL/6)F1 mice and in NOD-related strains made diabetes-resistant by congenic introduction of protective major histocompatibility complex (MHC) or non-MHC Idd region genes. Here, we tested the hypothesis that the genetic basis for the resistance of NOD mice to skin allograft tolerance also applies to islet allografts. Surprisingly, costimulation blockade induced permanent islet allograft survival in (NOD x C57BL/6)F1 mice but not in NOD mice. After costimulation blockade, islet allograft survival was prolonged in diabetes-resistant NOD.B6 Idd3 mice and shortened in diabetes-free C57BL/6 mice congenic for the NOD Idd3 variant. Islet allograft tolerance could not be induced in diabetes-resistant NOD.B10 Idd5 and NOD.B10 Idd9 mice. The data demonstrate that 1) NOD mice resist islet allograft tolerance induction; 2) unlike skin allografts, resistance to islet allograft tolerance is a genetically recessive trait; 3) an Idd3 region gene(s) is an important determinant of islet allograft tolerance induction; and 4) there may be overlap in the mechanism by which the Idd3 resistance locus improves self-tolerance and the induction of allotolerance.

Rights and Permissions

Citation: Diabetes. 2004 Aug;53(8):1972-8.

Related Resources

Link to article in PubMed

Journal Title

Diabetes

PubMed ID

15277375