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1992 Fiscal Year Final Research Report Summary

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
Keywordsadhesion molecules / extracellular matrix receptor / T cell activation / tolerance / integrins / CD4 / CD8 / CD2 / CD48 / LFA-1 / ICAM-1
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.

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1994-03-24  

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