| Project/Area Number |
01570269
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Osaka University Medical School |
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Principal Investigator |
ONO Shiro Osaka University Medical School, Lecturer, 医学部, 講師 (80127208)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1989: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Autoimmune disease / H-2-linked control / (NZBxNZW)F1 mice / Thymus graft / Radiation-induced bone marrow chimera / T-cell repertoire / 自己免疾疾患 / Hー2遺伝子 / (NZB×NZW)F1ヌ-ドマウス / H-2遺伝子 |
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| Research Abstract |
The development of human systemic lupus erythematosus (SLE) -like disease in (NZB x NZW) F1 (BWF1, H-2^<d/z>) mice was thought to be resulted primarily from their hyper-reactivity of B cell-function. However, We have demonstrated recently that congenitally athymic BWF1 nude mice fail to develop the disease, and that the engrafting thymus from BWF1 mice into BWF1 nude mice manifest the SLE-like disease. These results indicate the obligatory requirement fot thymus (T cells) in the development of autoimmune disease in BWF1 mice. Although it has been shown that H-2 gene products NZW mice play a crucial role in the onset of autoimmune disease in BWF1 mice, the mechanisms underlying the H-2-linked control are not clear at present.
This study was undertaken to investigate the possible association of thymic genotype with autoimmune manifestations in BWF1 mice by utilizing BWF1 nude mice engrafted with NZB (H-2^d), NZW (H-2^z), or BWF1 thymus. The development of SLE-like disease characterized by spontaneous product
ion of anti-ssDNA IgG antibodies and appearance of proteinuria was retarded in BWF1 nude mice engrafted with NZB thymus as compared to those engrafted with NZW or BWF1 mice, suggesting a crucial role of thymic H-2 genotype the disease. Moreover, T cells derived from lethally irradiated NZW or BWF1 mice reconstituted with BWF1 bone marrow cells ( BWF1->NZW or BWF1->BWF1 chimeras ) exhibited high helper activities capable of inducing in vitro anti-ssDNA IgG antibodies, while such a helper activity was not detected in T cells from BWF1->NZB chimeras.
The present results support the notion that the H-2-linked control of autoimmune disease in BWF1 mice is attributable to the influence of H-2 genotype of thymus on the generation of helper T cells responsible for auto-antibody production of IgG class.
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