Autoimmunity in HLA-DQ8 transgenic mice expressing granulocyte/macrophage-colony stimulating factor in the beta cells of islets of Langerhans.

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 A Beta degrees.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. A Beta degrees.NOD.DQ8 mice expressing GM-CSF in the pancreatic ss 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.

• Authors: Govindarajan Rajagopalan, Ashutosh K Mangalam, Moon M Sen, Shen Cheng, Yogish C Kudva, Chella S David
• Journal: Autoimmunity (Autoimmunity) Vol. 40 Issue 3 Pg. 169-79 (May 2007) ISSN: 0891-6934 [Print] England
• PMID: 17453715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DQ Antigens
• HLA-DQ8 antigen
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Autoimmune Diseases (genetics, pathology)
• Diabetes Mellitus, Type 1 (genetics, pathology)
• Granulocyte-Macrophage Colony-Stimulating Factor (biosynthesis, genetics)
• HLA-DQ Antigens (genetics)
• Insulin-Secreting Cells (immunology, metabolism)
• Mice
• Mice, Transgenic