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Elucidation of mechanism of NK cell activation

Research Project

Project/Area Number 11670312
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionChiba University

Principal Investigator

TAKI Shinsuke (2000)  Chiba University, Grad.Sch.of Med., Associate Professor, 大学院・医学研究科, 助教授 (50262027)

荒瀬 尚 (1999)  千葉大学, 大学院・医学研究科, 助手 (10261900)

Co-Investigator(Kenkyū-buntansha) YAMASAKI Sho  Chiba University, Grad.Sch.of Med., Assistant, 大学院・医学研究科, 助手 (40312946)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsNFAT / retrovirus / library / NK cell / lymphocyte activator / signal transducer / expression cloning / reporter gene / CD3ζ鎖 / FcγRIII / NKT細胞 / NK1.1 / diphthelia toxin / マウス
Research Abstract

NK cells play important roles in anti-tumor immune response. However, the exact mechanism for their activation still remains unclear. In this study, we have analyzed activation mechanism of NK cells using CD3ζ-deficient mice and a newly developed method for identifying signaling molecules. From the analysis of CD3ζ-deficient mice, we found that CD3ζ negatively regulate the expression and function of FcγRIII on NK cells. Next, we developed a new method using NFAT-GFP transfected reporter cells and unique CD8 chimera cDNA library, in which retrovirally infected reporter cells were crosslinked with anti-CD8 antibody and those become positive for GFP were cloned. cDNAs recovered from these cells included Igα, Igβ, CD3ε, ZAP70, Syk when a library prepared from spleen were used. On the other hand, FcRγ, DAP12, ZAP70 were identified from a library prepared from NK cells. These results show that this method is in fact a powerful method for cloning signaling molecules of lymphocytes. We named this method as NFAT Activating gene Cloning System (NACS). In addition to these already known molecules, we have identified several unknown molecules that activate NFAT-driven transcription upon crosslinking. In future, we will further analyze these newly cloned molecules to exploire the activation mechanism of NK cells.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Arase,H.: "Negative regulation of expression and function of Fc γ RIII byCD3 ζ in murine NK cells."J.Immunol.. 166. 21-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arase,H.: "The quantity of TCR signal determines positive selection and lineage commitment of T cells."J.Immunol.. 166. 6252-6261 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arase,H.: "Regulation of cell surface expression of CTLA-4 by secretionof CTLA-4-containing lysosomes upon activation of CD4^<C+>T cells."J.Immunol.. 165. 5062-5068 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arase,H.: "Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo Th cell responses."J.Immunol.. 164. 6113-6119 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arase,H.: "A Di-leucine signal in the ubiquitin moiety. Possible involvement in ubiquitination-mediated endocytosis."J.Biol.Chem.. 276. 26213-26219 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arase,H.: "CD8^+ T cell-mediated skin disease in mice lacking IRE-2, the transcriptional attenuator of interferon-α/β signaling."Immunity. 13. 643-655 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arase, K.: "Ablation of a specific cell population by the replacement of an uniquely expressed gene with a toxin gene."Proc.Natl.Acad.Sci.USA. 96. 9264 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Watanabe, N.: "The quantity of TCR signal determines positive selection and lineage commitment of T cells."J.Immunol.. 165. 6252 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iida, T.: "Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4 (+) T cells."J.Immunol.. 165. 5062 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hamano, Y.: "Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo Th cell responses."J.Immunol.. 164. 6113 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakatsu, F., Ohno, H.: "A Di-leucine signal in the ubiquitin moiety. Possible involvement in ubiquitination-mediated endocytosis"J.Biol.Chem.. 275. 26213 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arase, H.: "Negative regulation of expression and function of FcγRIII by CD3ζ in murine NK cells."J.Immunol.. 166. 21 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arase,H.: "Negative regulation of expression and function of Fc γ RIII byCD3 ζ in murine NK cells."J.Immunol.. 166. 21-25 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Arase,H.: "The quantity of TCR signal determines positive selection and lineage commitment of T cells."J.Immunol.. 166. 6252-6261 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Arase,H.: "Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4^<(+>T cells."J.Immunol.. 165. 5062-5068 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Arase,H.: "Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo Th cell responses."J.Immunol.. 164. 6113-6119 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Arase,H.: "A Di-leucine signal in the ubiquitin moiety. Possible involvement in ubiquitination-mediated endocytosis."J.Biol.Chem.. 276. 26213-26219 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Arase,H.: "CD8^+ T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-α/β signaling."Immunity. 13. 643-655 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Arase, K.: "Ablation of a specific cell population by the replacement of a uniquely expressed gene with a toxin gene"Proc. Natl. Acad. Sci.. 96. 9264-9268 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Park, S. Y.: "Resistance of Fc receptor-deficient mice to fatal glomerulonephritis"J. Clin. Inv.. 102. 1229-1238 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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