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細胞障害性リンパ球による標的細胞破壊機構の解明およびその制御

Research Project

Project/Area Number 11470090
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

奥村 康  順天堂大, 医学部, 教授 (50009700)

Co-Investigator(Kenkyū-buntansha) 榧垣 伸彦  順天堂大学, 医学部, 助手 (80317403)
八木田 秀雄  順天堂大学, 医学部, 助教授 (30182306)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Keywords細胞障害性リンパ球 / アポトーシス / TRAIL / TWEAK / Fasリガンド / TNF / 生体防御 / 抗腫瘍効果 / CTL / NK / FasL / パーフォリン / IFN / 細胞傷害活性
Research Abstract

前年度までに我々は、Fas ligand(FasL)やtumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL)といったアポトーシス誘導分子がキラー細胞による標的細胞破壊機構に関与することを、主としてin vitro実験系にて解析を行ってきた。本研究において我々は、TRAIL分子のin vivoにおける機能について解析した結果、肝NK細胞がIFN-γ刺激によって恒常的にTRAIL分子を発現し、TRAILに対して感受性を示す種々の癌細胞の肝臓転移に対して、抑制的に働くことをマウスモデルを用いて明かとした。さらに、新規TNFファミリー分子であるTWEAKの発現と免疫系における機能について、新たに樹立した抗ヒトTWEAKモノクローナル抗体(CARL-1)を用いて、ヒト末梢血T、B、NK細胞および単球上のTWEAKの発現を解析した結果、TWEAK分子が、IFN-γによって単球細胞上に選択的に発現誘導されること、および、IFN-γによって活性化された単球の標的細胞傷害機構にはTRAILやTNF-αに加え、TWEAKを介した経路も関与することをin vitro実験系にて明かとした。ある種の腫瘍に対しては、単球細胞がエフェクター細胞として重要であることが報告されており、TWEAKが、TRAILやTNF-αとともに単球細胞による抗腫瘍効果の一翼を担っている可能性が考えられた。

Report

(2 results)
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Akiba,H.: "Critical contribution of OX40 ligand to T helper cell type 2 differentiation in experimental leishmaniasis."J Exp Med. 191. 375 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nohara,C.: "Amelioration of Experimental Autoimmune Encephalomyelitis with Anti-OX40 Ligand Monoclonal Antibody : A Critical Role for OX40 Ligand in Migration, But Not Development, of Pathogenic T Cells."J Immunol. 166. 2108 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeda,K.: "Critical contribution of liver natural killer T cells to a murine model of hepatitis."Proc Natl Acad Sci U S A. 97. 5498 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsukada,N.: "Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal acute graft-versus-host disease in a murine model of allogeneic bone marrow transplantation."Blood. 95. 2434 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakayama,M.: "Involvement of TWEAK in interferon gamma-stimulated monocyte cytotoxicity."J Exp Med. 192. 1373 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeda,K.: "Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells."Nat Med. 7. 94 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsukada, N.: "Graft-versus-leukemia effect and graft-versus-host disease can be differentiated by cytotoxic mechanisms in a murine model of allogeneic bone marrow transplantation."Blood. 93. 2738-2747 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kayagaki, N.: "Type I interferons(IFNs) Regulate Tumor Necrosis Factor-related Apoptosis-inducing Ligand(TRAIL) Expression on Human T Cells : A Novel Mechanism for the Antitumor Effects of Type I IFNs."J. Exp. Med.. 189. 1451-1460 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitamura, H.: "The Naturai Killer T(NKT) Cell Ligand α-Galactosylceramide Demonstrates Its Immunopotentiating Effect by Inducing Interleukin(IL)-12 Production by Dendritic Cells and IL-12 Receptor Expression on NKT Cells."J. Exp. Med.. 189. 1121-1127 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kodama, T.: "Perforin-dependent NK cell cytotoxicity is sufficient for antimetastatic effect of IL-12."Eur. J. Immunol.. 29. 1390-1396 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akiba, H.: "CD28-Independent Costimulation of T Cells by OX40 Ligand and CD70 on Activated B Cells"J. Immunol.. 162. 7058-7066 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Seino, K.: "Soluble forms of CD95 and CD95 ligand after living related liver transplantaion."Transplantation. 67. 635-636 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakano, H.: "Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation."Proc. Natl. Acad. USA. 96. 9803-9808 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kayagaki, N.: "Expression and function of TNF-related apoptosis-inducing ligand on murine activated NK cells."J. Immunol.. 163. 1906-1913 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsue, H.: "Induction of antigen-specific immunosuppression by CD95L cDNA-transfected 'killer' dendritic cells."Nature Med.. 5. 930-937 (1999)

    • Related Report
      1999 Annual Research Report

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

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