| Project/Area Number |
07807038
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KANAI Yoshiyuki The University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (30012785)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | nucleobindin / autoimmune disease / apoptosis / nucleosome / anti-DNA antibody / ヌクレオバインディン |
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| Research Abstract |
It has been confirmed that the appearance of serum nucleosome (NS) together with apoptosis in the thymus in normal mice given nucleobindin (Nuc) or anti-CD3 antibody intraperitoneally (i. p.) could be reproducibly observed. However, the clearance of NS from circulation was retarded in mice give both Nuc and anti-CD3 antibody. This retardation was found to be due to the binding of Nuc to NS,suggesting that induction of autoimmunity by Nuc is responsible for longer retention of autoantigens in the circulation. In such cases, not only the increment of histone H1 and tyrosine-phosphorylation of 35-40kDa proteins but also the newly appearance of 20-30kDa proteins with pl 5.5-5.7 in 2D gel electrophoresis were observed. Because these were Nuc-associated new findings, I am extending the study for the elucidation of these molecule in terms of autoimmunity. The establishment of two T cell lines that are specific for Nuc was successful from BALB/c mice given Nuc continuously ; lines T4 and T8 were positive for CD4 and restricted to MHC (I-Ad). These lines will be useful for further analysis of systemic aoutoimmunity mechanisms. Taken together, I conclude as the role of Nuc in autoimmunity induction, as follows. 1) elevation of Nuc in the circulation due to metabolic failure. 2) release of nucleosome in to the circulation due to apoptosis in the thymus by Nuc. 3) Nuc bound with nucleosome induces helper T cells for anti-DNA antibody production.
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