Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II

Yogish C. Kudva, Govindarajan Rajagopalan, Raghavan Raju, Roshini S. Abraham, Michelle Smart, Julie Hanson, Chella S. David

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

To evaluate the contributions of DR3 and DQ8 to the etiopathogenesis of type 1 diabetes in a diabetes-predisposing milieu, we developed human leukocyte antigen (HLA) transgenic mice on the nonobese diabetic (NOD) background in the absence of the endogenous class II molecule, I-Ag7 and studied the incidence of both spontaneous and experimental (induced) autoimmune diabetes. Transgenic expression of HLA-DR3 and -DQ8 (either alone or in combination) did not confer susceptibility to spontaneous or cyclophosphamide-induced type 1 diabetes. Expression of I-Ag7 was mandatory for development of spontaneous or cyclophosphamide-induced diabetes. However, multiple low doses of streptozotocin could induce diabetes in all groups of mice independent of the class II molecules expressed. In unmanipulated mice, only islets from I-Ag7+/+ mice revealed significant intra-islet infiltration. Although a characteristic peri-insulitis/peri-ductulitis was present in Aβ0/NOD mice, islets from DR3, DQ8 and DR3.DQ8 double transgenic mice demonstrated significantly less infiltration. In conclusion, transgenic expression of HLA-DR3 and -DQ8 associated with predisposition to type 1 diabetes alone is not sufficient to induce spontaneous diabetes in NOD mice lacking endogenous class II molecules.

Original languageEnglish (US)
Pages (from-to)987-999
Number of pages13
JournalHuman Immunology
Volume63
Issue number11
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

Keywords

  • Diabetes
  • HLA-DQ8
  • HLA-DR3
  • Insulitis
  • Transgenes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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