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 language | English (US) |
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Pages (from-to) | 987-999 |
Number of pages | 13 |
Journal | Human Immunology |
Volume | 63 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2002 |
Externally published | Yes |
Keywords
- Diabetes
- HLA-DQ8
- HLA-DR3
- Insulitis
- Transgenes
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology