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Sudies on the differention and activation mechanisms of T cell via lymphocye functioning antigen (LFA).

Research Project

Project/Area Number 04404035
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionJuntendo University

Principal Investigator

OKUMURA Ko  Juntendo Univ. Sch. of Med.Prof., 医学部, 教授 (50009700)

Co-Investigator(Kenkyū-buntansha) AZUMA Miyuki  Juntendo Univ. Sch. of Med.Assistant Prof., 医学部, 助手 (90255654)
KATO Kazunori  Juntendo Univ. Sch. of Med.Assistant Prof., 医学部, 助手 (60233780)
RA Chisei  Juntendo Univ. Sch. of Med.Associate Prof., 医学部, 講師 (60230851)
YAGITA Hideo  Juntendo Univ. Sch. of Med.Associate Prof., 医学部, 助教授 (30182306)
屋部 登志雄  順天堂大学, 医学部, 助手 (50239836)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsCD2 / CD48 / CD86 / CD80 / tolerance / allograft rejection / auto immune disease / monoclonal antibody / CD28 / 移植拒絶 / T cell / LAK / Thy-1 / ヘルパーT細胞 / VLA / 免疫寛容 / 拒絶反応
Research Abstract

We performed the study to know how lymphocyte function associated antigens (LEA) on T cell are involved in various kind of immune responses. To analyzes it's mechanisms, we at first reported the effect of in vivo administration on the induction of tolerance by using mouse heart allograft experimental system. Then, it was revealed that absence of costimulatory signals from LFA-1 could induce T cell anergy. To investigate more detailed mechanisms of T cell tolerance, we further analyzed the role of other LFA in terms of T cell anergy induction. Then, we further analyzed the role of other LEA on T cell as well as those ligand molecules on antigen presenting all (APC). On the way of study, we could identify CD48 as unknown ligand of mouse CD2. By using monoclonal antibody to those molecules which we established, we could examine the biological significance of CD2 and CD48/LFA-3 pathway. Regarding to the signals from CD28 of T cell, we succeeded to identify unknown ligand on APC and name B70 (CD86). By using cDNA of B70 as well as monoclonal antibody, we could expand the study how CD28 and CD80/CD86 pathway is important to understand the intiation of T cell immune reponse as well as anergy induction and/or maintenance of T cell torelance. Especially using in vivo experimental systems, the administration of antiCD80 and antiCD86 could induce permanent torelance in the donor received allograft.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Isobe,M.,: "Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1." Science. 255. 1125-1127 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi,K.,: "CD4 and CD8 regulate interleukin 2 responses of T cells." Proc.Natl.Acad.Sci.89. 5557-5561 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato,K.: "CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation" J.Exp.Med.176. 1241-1249 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyake,S.: "β1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients." J.Exp.Med.177. 863-868 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Azuma,M.: "B70 antigen is a second ligand for CTLA-4 and CD28." Nature. 366. 76-79 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hanabuchi,S.: "Fas and its ligand in a general mechanism of T cell-mediated cytotoxity." Proc Natl.Acad.Sci.,USA. 91. 4930-4934 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yagita,H.: "Role of perforin in lymphocyte-mediated cytolysis." Adv.Immunol., 27 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yagita,H.: "The role of adhesion molecules in triggering effector mechanisms.In:Proceedings of the first green cross international symposium “Immunology for tomorrow" 1992 - molecular basis of Immune responses." Academic Press,Inc, 10 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Isobe, M.: "Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1." Science. 255. 1125-1127 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi, K: "CD4 and CD8 regulate interleukin 2 reponses of T cells." Proc. Natl. Acad. Sci.89. 5557-5561 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kato, K.: "CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation" J.Exp. Med.176. 1241-1249 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyake, S.: "beta1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients." J.Exp.Med.177. 863-868 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Azuma, M.: "B70 antigen is a second ligand for CTLA-4 and CD28." Nature. 366. 76-79 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hanabuchi, S.: "Fas and its ligand in a general mechanism of T cellmediated cytotoxity." Proc. Natl. Acad. Sci.USA. 91. 4930-4934 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yagita, H.: "Proceedings of the first green cross international symposium "Immunology for tomorrow" 1992- molecular basis of Immune responses." Academic Press, Inc.59-69 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hanabuchi,S.: "Fas and its ligand in a general mechanism of T cell‐mediated" Proc.Natl.Acad.Sci.,USA,. 91. 4930-4934 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Seko,Y.: "Perforin‐secreting killer cell infiltration and expression of a 65‐kD heat‐shock protein in aortic tissue of patients with takayasu's arteritis." J.Clin.Invest.93. 750-758 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Caux,C.: "B70/B7‐2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells." J.Exp.Med.180. 1841-1847 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kojima,H.: "Two Distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes." Immunity. 1. 357-364 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyake,S.: "Identification of collagen and laminin receptor integrins on murine T lymphocytes." Eur.J.Immunol.24. 2000-2005 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yanagihara,Y.: "Recombinant soluble form of the human high‐affinity immunoglobulin E(IgE)receptor inhibits IgE production through its specific binding to IgE‐bearing B cells." J.Clin.Invest.94. 2162-2165 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kato,K.: "Identification of a T cell surface signal-transducing glycoprotein sgp-60,as CD48 that is a counter-receptor for mouse CD2." Eur.J.Immunol.23. 1412-1415 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Azuma,M.: "B70 antigen is a second ligand for CTLA-4 and CD28." Nature. 366. 76-79 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kato,K.: "CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation." J.Exp.Med.176. 1241-1249 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hanabuchi,S.: "Fas and its ligand in a general mechanism of T cell-mediated cytotoxity." Proc.Natl.Acd.Sci.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yagita.H.: "The role of adhesion molecules in triggering effector mechanisms.In:Proceedings of the first green cross international symposium "Immunology for tomorrow"1992-molecular basis of Immune responses." Academic Press,Inc.:. 59-69,

    • Related Report
      1993 Annual Research Report
  • [Publications] Isobe,M.: "A short course of anti-ICAM/anti-LFA-1 treatment leads to specific acceptance of cardiac allograft." Science. 255. 1125-1127 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takahashi,K.: "CD4 and CD8 regulate interleukin 2 responses of T cells. Proc. Natl." Acad.Sci.89. 5557-5561 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kawasaki,A.: "Expression of perforin in murine natural Killer cells and cytotoxic T lympohocytes vivo." Eur.J.Immunol.22. 1215-1219 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kato,K.: "CD48 is a counter-recepter for CD2 and envoloved in T cell activation." J.Exp.Med.176. 1241-1249 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kato,K.: "idenification of a T cell surface signal-turansducing glycoprotein, sgp-60, as CD48 that is a counter-receptor for mouse CD2." Eur.J.Immunol.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miyake.,S.: "β1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression synovial fluid cells of theumatoid arthritis patients." J.Exp.Med.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 0kumura,K.: "Intractable vasculitis syndromes." Hokkaido Univ.Press, 284 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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