Title

Autoimmune diabetes and resistance to xenograft transplantation tolerance in NOD mice

UMMS Affiliation

University of Massachusetts Medical School Department of Medicine, Division of Diabetes; Department of Pathology

Publication Date

12-24-2004

Document Type

Article

Subjects

Animals; Diabetes Mellitus, Type 1; Female; Graft Rejection; Graft Survival; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Rats; Transplantation, Heterologous; Treatment Failure

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Costimulation blockade induces prolonged rat islet and skin xenograft survival in C57BL/6 mice. Nonobese diabetic (NOD) mice, which are used to model human autoimmune diabetes, are resistant to costimulation blockade-induced allograft tolerance. We tested the hypothesis that NOD mice would also be resistant to costimulation blockade-induced rat xenograft tolerance. We report that rat islet xenograft survival is short in spontaneously diabetic NOD mice treated with a tolerizing regimen of donor-specific transfusion and anti-CD154 antibody. Rat islet xenograft survival is only marginally longer in chemically diabetic NOD mice treated with costimulation blockade but is prolonged further in NOD Idd congenic mice bearing C57-derived chromosome 3 loci. Reciprocally, the presence of NOD-derived chromosome 3 loci shortens islet xenograft survival in tolerized C57BL/6 mice. Islet xenograft survival is longer in tolerized NOD.CD4a(-/-) and (NOD x C57BL/6)F1 mice than in NOD mice but still much shorter than in C57BL/6 mice. Skin xenograft survival in (NOD x C57BL/6)F1 mice treated with costimulation blockade is short, suggesting a strong genetic resistance to skin xenograft tolerance induction. We conclude that the resistance of NOD mice to xenograft tolerance induction involves some mechanisms that also participate in the expression of autoimmunity and other mechanisms that are distinct.

Rights and Permissions

Citation: Diabetes. 2005 Jan;54(1):107-15.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Diabetes

PubMed ID

15616017