Prevention of autoimmune insulitis by expression of I-E molecules in NOD mice.
The NOD (non-obese diabetic) mouse spontaneously develops insulin-dependent diabetes mellitus (IDDM) characterized by autoimmune insulitis, involving lymphocytic infiltration around and into the islets followed by pancreatic beta (beta) cell destruction, similar to human IDDM. Genetic analysis in breeding studies between NOD and C57BL/6 mice has demonstrated that two recessive genes on independent chromosomes contribute to the development of insulitis. One of the two recessive diabetogenic genes was found to be linked to the major histocompatibility complex (MHC). This is of interest, because the NOD strain has a unique class II MHC: it does not express I-E molecules as no messenger RNA for the alpha-chain of I-E is visible in Northern blot analysis; I-A molecules are not detected with any available monoclonal antibodies or by allo-reactive or autoreactive T-cell clones, although their expression is demonstrated with a conventional antiserum to Ia antigens. To examine whether the unusual expression of class II MHC molecules may be responsible for the development of autoimmune insulitis, we attempted to express I-E molecules in NOD mice selectively, without introducing other genes on chromosome 17 by using I-E-expressing C57BL/6 (B6(E alpha d)) transgenic mice. We report here that the expression of I-E molecules in NOD mice can prevent the development of autoimmune insulitis.
Nishimoto
H
H
Kikutani
H
H
Yamamura
K
K
Kishimoto
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014170:Transformation, Genetic
D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen