| Project/Area Number |
13470072
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
KIKUTANI Hitoshi Osaka Univ., Res. Inst. for Microbial Diseases, Prof., 微生物病研究所, 教授 (80161412)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Kenji Osaka Univ., Res. Inst. for Microbial Diseases, Assistant Prof., 微生物病研究所, 助手 (80294122)
KUMANOGOH Atsushi Osaka Univ., Res. Inst. for Microbial Diseases, Assistant Prof., 微生物病研究所, 助手 (10294125)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2001: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | co-stimulatory molecules / B cell / CD40 / CD100 / CD72 / Sema4A / T cell / セマフォリン / 自己免疫 / 樹状細胞 / Tim2 / 補助刺激分子 / 免疫 |
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| Research Abstract |
1) Role of CD 100 in T cell activation : CD100-deficient mice are resistant to experimental autoimmune encephalomyelitis (EAF) because generation of antigen-specific T cells is severely affected in the absence of CD100. Recombinant soluble CD100 enhances activation and maturation of dendritic cells. In addition, CD100-deficient dendritic cells display poor responses to various stimuli such as LPS and anti-CD40. These findings indicate that CD100 is critically involved in activation and maturation of antigen presenting cells such as dendritic cells, which is necessary for T cell activation.
2) Function of Sema4A expressed on dendritic cells : A novel class IV semaphorin, Sema4A, which is expressed on dendritic cells and B cells but not resting T cells, is cloned. Recombinant soluble Sema4A enhances in vitro activation and differentiation of T cells induced by anti-CD3 and anti-CD28. Administration of anti-Sema4A mAb into MOG-immunized mice can block not only generation of MOG-specific T cells but also induction of EAE. The observations indicate that Sema4A is essential for T cells activation in vitro and in vivo.
3) Isolation of Sema4A receptor expressed on T cells : Soluble Sema4A binding is detectable on activated T cells and some T cells lines. Tim-3 has been isolated from EL-4 T cells by expression cloning. Soluble Sema4A can bind to Tim-3 transfected cells but not Tim-1 transfected cells. Stimulation with soluble Sema4A induces tyrosine-phosphorylation of Tim-2, suggesting that Tim-2 may deliver a positive signal.
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