Effects of transgenic mixed-haploptype MHC class II molecules AαdAβz on autoimmune disease in New Zealand mice
| Autor: | Massaki Abe, Hiromichi Tsurui, Masanori Awaji, Shin Akakura, Shingo Nozawa, Hiroyuki Nishimura, Yudai Gotoh, Juichi Saito, Toshikazu Shirai, Masao Kimoto, Miyoko Tokushima, Sachiko Hirose, Sho Ishikawa |
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| Rok vydání: | 1996 |
| Předmět: |
Genetically modified mouse
MHC class II biology Transgene T cell Immunology Lupus nephritis General Medicine medicine.disease Major histocompatibility complex Immune system medicine.anatomical_structure immune system diseases biology.protein medicine Immunology and Allergy Antibody skin and connective tissue diseases |
| Zdroj: | International Immunology. 8:967-976 |
| ISSN: | 1460-2377 0953-8178 |
| Popis: | The MHC haplotype heterozygosity (H-2d/H-2z) acts as one major predisposing genetic element for autoimmune disease resembling systemic lupus erythematosus (SLE) in the F1 hybrid of NZB (H-2d) and NZW (H-2z) mice. To determine a possible role of mixed-haplotype A molecules, we introduced a transgene A beta z into H-2d/H-2d homozygous (NZB x NZW.H-2d)F1 mice, in which, compared with the original H-2d/H-2z heterozygotes, the incidence and titer of IgG anti-DNA antibodies, serum levels of nephritogenic retroviral gp70/anti-gp70 immune complexes (ICs) and the associated incidence of IC-type lupus nephritis were reduced. Evidence for the formation of mixed-haplotype A alpha d A beta z molecules in the transgenic mice was obtained by A beta z molecule expression on the cell surface of splenic B cells and macrophages, thymic epithelial cells and mature B cells in the bone marrow. A alpha d A beta z-restricted T cell clones showed good proliferative responses to spleen cells from the transgenic mice, to an extent much larger than seen in cells from the original (NZB x NZW)F1 mice, suggesting that the expression of functional A alpha d A beta z molecules on cells in transgenic mice is considerably high. Compared with findings in transgene-negative littermates and the original (NZB x NZW)F1 mice, the A beta z transgene to a greater extent promoted serum levels of IgM anti-double-stranded (ds) DNA antibodies and IgM anti-gp70/gp70 ICs in the transgenic mice. None the less, the production of IgG anti-dsDNA antibodies and IgG anti-gp70/gp70 ICs as well as the development of renal disease was markedly suppressed. Possible mechanisms of such effects of the transgene are discussed. |
| Databáze: | OpenAIRE |
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