title: Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class I Ld molecules.
abstract: Nonobese diabetic (NOD) mice spontaneously develop a T-cell-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in humans. NOD mice were shown to express major histocompatibility complex class I Kd and Db antigens. To examine the possible involvement of major histocompatibility complex class I molecules in the development of autoimmune insulitis, we attempted to express a different type of class I molecule in NOD mice by crossing C57BL/6 mice transgenic for the class I Ld gene with NOD mice. The backcross progeny expressed the Ld antigen on the peripheral blood lymphocytes at a level comparable with that of the BALB/c mice. The cell surface expression of endogenous class I and class II antigens on the peripheral blood lymphocytes was not affected. Analysis of these mice revealed that the expression of the class I Ld antigen significantly reduced the incidence of insulitis at 20 weeks of age. In situ hybridization of a biotinylated probe on mouse chromosomes showed that the Ld transgene was located in the E area of chromosome 6 with which no genetic linkage to insulin-dependent diabetes mellitus was demonstrated. These results suggest that the NOD-type class I molecules are involved in the development of insulitis in NOD mice.
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Toyonaga
authors.forename: J
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: K
authors.initials: K
authors.lastname: Yamamura
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000276:immunology*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology*; D008822:Mice, Transgenic
chemical_list: D006183:H-2 Antigens