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Molecular biological study on intercellular adhesion molecules involved in activation and differentiation of hematopoietic cells.

Research Project

Project/Area Number 02454195
Research Category

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

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionJuntendo University School of Medicine

Principal Investigator

YAGITA Hideo  Juntendo University, School of Medicine, Associate Professor, 医学部, 助教授 (30182306)

Co-Investigator(Kenkyū-buntansha) OKUMURA Ko  Juntendo University, School of Medicine, Professor, 医学部, 教授 (50009700)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1990: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywordsadhesion molecules / extracellular matrix receptor / T cell activation / tolerance / integrins / CD4 / CD8 / CD2 / CD48 / LFA-1 / ICAM-1 / LFAー1 / ICAMー1 / T細胞分化 / CD_2 / CD11a / 18 / CD54
Research Abstract

(1)We revealed that CD4 and CD8 regulate IL-2 response of T cells via activation of p56^<lck> associated with them.
(2)We demonstrated that CD2-mediated signal plays an important role in T and NK cell activation.
(3)We revealed that CD48 is the predominant ligand for mouse CD2.
(4)We also demonstrated that CD48 is the second ligand for human CD2 other than LFA-3.
(5)We found that administration of anti-CD2 and anti-CD48 monoclonal antibodies led to a specific acceptance of mouse cardiac allografts.
(6)We found that administration of anti-LFA-1 and anti-ICAM-1 monoclonal antibodies led to a specific acceptance of mouse and rat cardiac allografts, which resulted from the induction of allospecific peripheral tolerance by clonal anergy. We also found that anti-VLA-4 and anti-VCAM-1 monoclonal antibodies had a similar effect although it was less efficient.
(7)We found that administration of anti-LFA-1 and anti-ICAM-1 monoclonal antibodies suppressed the pathogenesis of adjuvant arthritis in rats, collagen-induced arthritis in mice, and diabetes in NOD mice.
(8)We found that anti-VLA-4 and anti-VCAM-1 monoclonal antibodies specifically inhibited erythropoiesis in vitro and in vivo.
(9)We established monoclonal antibodies to mouse and rat vitronectin receptor, VLA-4, and VLA-5, and demonstrated that the interaction with fibronectin mediated by these integrins are critically involved in regulating T and mast cell activation.
(10)We established monoclonal antibodies to mouse VLA-1, VLA-2, VLA-3, and VLA-6, and examined the expression and function of these collagen and/or laminin receptors on hematopoietic cells.
(11)We revealed that beta_1 integrin-mediated interaction with extracellular matrix proteins regulates inflammatory cytokine gene expression in synovial fluid mononuclear cells of rheumatoid arthritis patients.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 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
      1992 Final Research Report Summary
  • [Publications] Takahashi K.: "CD4 and CD8 regulate IL-2 response of T cells." Proc.Natl.Acad.Sce.USA. 89. 5557-5561 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kato K.: "CD48 is a counter-receptor for mouse CD2 and 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
      1992 Final Research Report Summary
  • [Publications] Kakimoto K.: "The effect of anti-adhesion molecule antibody on the development of collagen-induced arthritis." Cell.Imm.unol.142. 326-337 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Miyake,S.: "β_1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients." J.Exp.Med.(1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Arulanandam A.R.N.: "A soluble multimeric recombinant CD2 protein identifies CD48 as a low affinity ligand for human CD2:Divergence of CD2 ligands during the evolution of man and mouse." J.Exp.Med.(1993)

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

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kato,K. et al.: "CD48 is a counter-receptor for mouse CD2 and involoved 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
      1992 Final Research Report Summary
  • [Publications] Kakimoto,K. et al.: "The effect of anti-adhesion molecule antibody on the development of collagen-induced arthritis." Cell. Immunol.142. 326-337 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Miyake,S. et al.: "beta1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients" J. Exp. Med.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Arulanandam,A.R.N. et al.: "A soluble multimeric recombinant CD2 protein identifies CD48 as a low affinity ligand for human CD2: Divergence of CD2 ligands during the evolution of man and mouse." J. Exp. Med.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 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)

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

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

    • Related Report
      1992 Annual Research Report
  • [Publications] Kakimoto,K.: "The effect of anti-adhesion molecule antibody on the development of collagen-induced arthritis." Cell.Immunol.142. 326-337 (1992)

    • Related Report
      1992 Annual Research Report
  • [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.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Arulanandam,A.R.N.: "A soluble multimeric recombinant CD2 protein identifies CD48 as a low affintity ligand for human CD2: Divergence of CD2 ligands during the evolution of man and mouse." J.Exp.Med.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Nakamura: "Acitivation of a NK clone upon target cell binding via CD2." Eur.J.Immunol.21. 831-834 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Takahashi: "Anitigenーindependent T cell activation mediated by a VLAーlike extracellular matrix receptor." Eur.J.Immunol.21. 1559-1562 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] H.Ohno: "Induction of negative signal through CD2 during antigenーspecifie T cell activation." J.Immunol.147. 2100-2106 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.kato: "A dhesion molecules on murine lymphokineーacitivated killer cells responsible for target cell killing:A role of CD2." Jpn.J.Cancer Res.82. 1139-1144 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Iigo: "ICAMーIーdependent pathway is critically involved in the pathogensis of aduuvant arthrites in rats." J.Immunol.

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Isobe: "A Short course of antiーICAMー1/antiーLFAー1 treatment leads to specific acceptance of cardiac allograft." Science.

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Shirai: "The expanded populations of CD4^-CD8^- T cell receptor α/β^+ T cell associated with the lpr and gld mutations are CD2^-" J.immunol.144. 3756-3761 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Nakamura: "Relative contribution of CD2 and LFAー1 to murine T and NK cell functions." J.immunol.145. 3628-3634 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Takahashi: "A murine very late activation antigenーlike extracellular matrix receptor involved in CD2^- and lymphocyte functionーassociated antigenー1ーindependent killerーtarget cell interaction." J.immunol.145. 4371-4379 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Nishimura: "Thymic stromal cell clone with nursing activity supports the growth and differentiation of murine CD4^+8^+ thymocytes in vitro." J.immunol.145. 4012-4017 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Nakamura: "Activation of a NK clone upon target cell binding via CD2." Eur.J.Immunol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Shiohara: "Evidence for involvement of lymphocyte tunctionーassociated antigen 1 in T cell migration to epidermis." J.Immunol.(1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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