Immunogenetic analysis of beta-cell autoimmunity in NOD mice. Relationship of insulitis to T-lymphocyte-receptor beta nod and A beta nod genes.
An early molecular event in the evolution of insulin-dependent diabetes in humans and NOD mice appears to involve the interaction of MHC class II molecules, beta-cell autoantigen-derived peptides, and receptor molecules of helper T lymphocytes. To examine the influence of T-lymphocyte-receptor beta-genes on the development of beta-cell autoimmunity, (NOD x NZW)F1 x NOD backcrossed (BC) mice were studied for the development of insulitis, because insulitis is the pathognomonic histological lesion of autoimmune diabetes. Heterozygosity for H-2nod was permissive for the development of pancreatic interstitial inflammation and peri-islet insulitis, whereas homozygosity for H-2nod was highly associated with insulitis. However, (NOD x NZW)F1 x NOD BC mice developed insulitis regardless of homozygosity or heterozygosity for T-lymphocyte receptor beta nod. Therefore, in our study, T-lymphocyte receptor beta nod did not function as an autosomal-recessive beta-cell autoimmunity gene.
Winter
W E
WE
Department of Pathology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville 32610.
Shimpo
K
K
Obata
M
M
Yamada
K
K
Luchetta
R
R
D000818:Animals; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D002465:Cell Movement; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009765:Obesity; D010182:Pancreatic Diseases / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta
D006183:H-2 Antigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta