| Project/Area Number |
11470087
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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.Microbial Diseases, Prof., 微生物病研究所, 教授 (80161412)
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| Co-Investigator(Kenkyū-buntansha) |
KUMANOGOH Atsushi Osaka Univ., Res.Inst.Microbial Diseases, Assist.Prof., 微生物病研究所, 助手 (10294125)
YOSHIDA Kenji Osaka Univ., Res.Inst.Microbial Diseases, Assist.Prof., 微生物病研究所, 助手 (80294122)
安居 輝人 大阪大学, 微生物病研究所, 助手 (60283074)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2000: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1999: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | CD100 / CD40 signal / LPS / semaphorin / CD100 deficient mouse / T cell / CD72 / SHP1 / トランスジェニックマウス / EB-ウイルス / LMP1 |
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| Research Abstract |
1) CD40 was found to play a role in LPS responses in a ligand-independent manner because macrophages and B cells from CD40-deficient mice but not from CD40 ligand-deficient mice displayed impaired responses to LPS.Biochemical studies revealed that CD40 was associated with TLR4 upon stimulation with LPS, suggesting that CD40 is involved in LPS signaling as one of LPS receptor components.
2) CD100 was found to induce dephosphorylation of its lymphocyte receptor, CD72, and dissociation of a tyrosine phosphatase, SHP1 from CD72. This finding indicates that CD100 turns off negative signaling of CD72, resulting in augmentation of B cell activation.
3) CD100-deficient mice showed not only poor B cell responses but also impaired T cell priming. Furthermore, it was found that impaired T cell priming was due to a defect of activation of antigen presenting cells such as dendritic cells in the absence of CD100.
4) We demonstrated that CD100 was proteolytically cleaved and released from T and B cells as functional soluble CD100 upon activation of cells. Serum levels of soluble CD100 increased after immunization of normal mice or after the onset of autoimmune diseases of MRL/lpr mice. Furthermore, serum levels of soluble CD100 were found to well correlate with titers of specific antibodies or titers of auto-antibodies in these mice.
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