title: Non-diabetogenic insulitis in NOD<-->B10.GD allophenic mice in spite of permissive class I MHC antigens.
abstract: Allophenic mice (embryo aggregation mouse chimeras) enable us to dissect the process of spontaneous autoimmunity under physiological conditions. Our previous experiments showed that the autoimmune process in allophenic mice of the NOD<-->C57B1/6 strain combination does not progress from insulitis to diabetes. One possible explanation for this protection is that H-2 Kd-restricted CD8+ T cells kill only NOD beta cells (Kd,Db) in the chimeric islets, while the B6 beta cells (Kb,Db) are spared from destruction. To test this hypothesis we analysed 22 NOD<-->B10.GD chimeras in which the class I MHC are shared by both parental strains. Therefore all the beta cells in these chimeras express H-2 Kd molecules. Ten allophenic mice were killed at 7 weeks and studied for early pathology. No evidence for intra-islet infiltration was obtained at this age, suggesting that the autoimmune process in NOD<-->B10.GD chimeras is slower than in NOD mice. Twelve chimeras were followed up for 1 year for disease development and all failed to progress to full-blown diabetes, despite the occurrence of intra-insulitis in six out of 12 mice. The lack of disease in NOD<-->B10.GD chimeras demonstrates that class I MHC chimerism does not account for diabetes resistance in NOD-allophenic mice.
authors.affiliation: Department of Applied Cell and Molecular Biology, Umeå University, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Colucci
authors.forename: U
authors.initials: U
authors.lastname: Dahl
authors.forename: L
authors.initials: L
authors.lastname: O'Reilly
authors.forename: A
authors.initials: A
authors.lastname: Cooke
authors.forename: P
authors.initials: P
authors.lastname: Chandler
authors.forename: E
authors.initials: E
authors.lastname: Simpson
authors.forename: T
authors.initials: T
authors.lastname: Matsunaga
mesh_terms: D000818:Animals; D002678:Chimera / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006183:H-2 Antigens / Q000235:genetics*; D064532:Histocompatibility Antigen H-2D; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics; D013154:Spleen / Q000166:cytology
chemical_list: D006183:H-2 Antigens; C024755:H-2K(K) antigen; D064532:Histocompatibility Antigen H-2D