Abstract
Type 1 diabetes (T1D) is a polygenic autoimmune disease with a strong HLA association particularly, HLA-DQ8. We investigated whether islet-specific expression of granulocyte/macrophage colony-stimulating factor (Ins.GM-CSF) in Aβ°.NOD.DQ8 mice (HLA-DQ8 transgenic mice on a NOD background lacking endogenous mouse MHC class II molecules) would predispose to development of spontaneous autoimmune diabetes. Aβ°.NOD.DQ8 mice expressing GM-CSF in the pancreatic β cells (8+ G+) as well as litter mates lacking either HLA-DQ8 (8- G+) or GM-CSF (8+ G-) or both (8-G-) exhibited insulitis and sialadenitis of varying degrees. But none of the mice progressed to develop T1D. Other than the marked mononuclear cell infiltration in livers of mice expressing GM-CSF irrespective of HLA-DQ8 expression (8+ G+ or 8- G+), no other changes were observed in the animals. Thus, we have shown for the first time that expression of HLA-DQ8 in the diabetes-predisposing mileu of NOD genetic background is not sufficient to predispose to development of autoimmune diabetes even when the potent immunostimulatory cytokine, GM-CSF is expressed in the pancreatic islets.
Original language | English (US) |
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Pages (from-to) | 169-179 |
Number of pages | 11 |
Journal | Autoimmunity |
Volume | 40 |
Issue number | 3 |
DOIs | |
State | Published - May 2007 |
Keywords
- Autoimmunity
- Diabetes
- GM-CSF
- HLA-DQ8
- Transgenic mice
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology