| Project/Area Number |
09670342
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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 | Juntendo University |
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Principal Investigator |
KOBATA Tetsuji Dept Immunol, Juntendo U Sch Med Asst Professor, 医学部, 講師 (10205445)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIOKA Kusuki Inst Med Sci, St.Marianna U Sch Med Professor, 難治研, 教授 (60049070)
OKUMURA Ko Dept Immunol, Juntendo U Sch Med Professor, 医学部, 教授 (50009700)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | autoimmunity / Fas / FasL / gld mice / apoptosis / self-tolerance / bone marrow transplantation / gene therapy |
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| Research Abstract |
Fas (CD95) ligand (L) is a death factor that binds to its receptor, F'as, andinduce apoptotic cell death, a crucial process in self-tolerance. gid(generalized lymphoproliferative disorder) mice, which have a point mutation in the FasL gene, develop spontaneous systemic autoirnmune syndromes characterized by hypergammaglobulinemia and lymphoid hyperplasia owing to accumulation of abnormal B220+CD3+ cells. In this study, we examined the effect of bone marrow transpiantion and FasL gene transfer on autoimmunity in gld mice to determine the role of apoptosis via Fas/FasL interactions in inducing and maintaining self-tolerance in vivo. Transplantation of wild-type bone marrow cells or administration of cells transfected with the FasL gene into old gld mice resulted in normalization of the above autoimmune symptoms. Cells sensitive to Fas-mediated apoptosis in gld mice resided not only among abnormal B22+CD3+ cells but also among conventional lymphocytes. More importantly, histological analysis revealed that cells in the spleen, lymph nodes and thymus frequently underwent apoptosis in recipient gld mice.
These results indicate that apoptosis via Fas/FasL interactions can directly eliminate pathogenic cells responsible for autoimmunity in the periphery and possibly in the thymus and that bone marrow transplantation and gene transfer of FasL may represent a new therapeutic strategy for autoimmunity caused by the FasL dysfunction.
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