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1996 Fiscal Year Final Research Report Summary

Molecular mechanisms of immune diseases.

Research Project

Project/Area Number 05272105
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionJuntendo University

Principal Investigator

OKUMURA Ko  School of Medicine, Juntendo University, Professor, 医学部, 教授 (50009700)

Co-Investigator(Kenkyū-buntansha) WATANABE Takeshi  Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (40028684)
NISHIMURA Yasuharu  Kumamoto University Graduate School of Medicine Sciences, Professor, 大学院・医学研究科, 教授 (10156119)
YODOI Junji  Institute for Virus Research, Kyoto University, Professor, ウィルス研究所, 教授 (80108993)
TAKATSU Kiyoshi  The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (10107055)
SHIRAI Toshikazu  School of Medicine, Juntendo University, Professor, 医学部, 教授 (30115860)
Project Period (FY) 1993 – 1995
Keywordsgene / signal transduction / autoantibody / B cell / MHC / transplantation / HIV
Research Abstract

All members of this group are involved in the analysis of the relationships between immune dysfunction and disease on a genetic level. From antibodies and thymocytes to signal transduction mechanisms, this group study a wide range of subjects related to pathological causation. 1.) This group discovered the existence of linkage between an unusual MHC haplotype and the abnormal increase in B1 cells, which are important autoimmune antibody secreting B cells. They also reported that the novel gene, which was dubbed Imh-1, is closely linked to the TNF receptor family located on the end of the 4th chromosome. In addition, the group found that the Mott-1 gene, expressed in Mott cells, which are terminally differentiated from B1 lineage cells and present in patients with immune diseases and BCLL,is linked to the Imh-1 locus on the 4th chromosome. 2.) This group reported that B Cell specific bluton kinase (Brk) and JAK2 kinase can be activated via stimulation with IL5. The group also reported t … More hat irregularities in the IL-5R signal transduction pathway are responsible for the weak response of B cells to IL-5 stimulation in XID mice. 3.) This group was successful in cloning the gene which encodes CD86, a molecule which functions as a costimulatory molecule for T cell activation. By decreasing CD28/CD80 and CD86 signal expression, specific tolerance can be induced. In animal models of SLE,rheumatoid arthritis and atopic dermatitis which already show abnormal immune reactivity, they observed a significant suppression of the abnormal immune reactivity by decreasing CD28/CD80 and CD86 signal expression. 4.) In its continued investigation of the role of intracellular signaling in the activation of lymphocytes, this group, by developing Lyn kinase and HS1 deficient mice, analyzed the effects of dysregulation of these molecules on a molecular level. The group also determined the structure of tyrosine phosphory lated HS1 protein. 5.) This group showed that substitution of amino acids in sntigenic peptides altered the immune response to the antigenic peptides. 6.) This group demonstrated that HIV env protein gp 160 can bind to CaM,producing a dimmer that causes apoptosis due to intracellular accumulation of Ca2+. Furthermore, this group observed that binding of the env protein gp 120 to CD4 cells causes FasL production and an induction of apoptosis in CD4 and CD8 cells. Less

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Seino K.: "Anti-tumor effect of locally produced Fas ligand." Nature Medicine. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaneko Y.: "CD40-mediated stimulation of B1 and B2 cells:implication in autoantibody production in murine lupus." Eur.J.Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato K.: "Local production of IL-12 p40 suppresses Th1-mediated immune responses and prevents allogeneic myoblast rejection." Proc.Natl.Acad.Sci,USA. 93. 9085-9089 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida T.: "Defective B-1 cell development and impaired immunity against angiostronglylus cantonensis in IL-5R deficient mice." Immunity. 4. 483-494 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kayagaki N.: "Metalloproteinase-mediated release of human Fas ligand." J.Exp.Med.182. 1777-1783 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kikuchi Y.: "CD38 ligation induces Btk activation and enhanced expression of IL-5 receptor a chain." Proc.Natl.Acad.Sci.USA. 92. 10879-10883 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda T.: "Restoration of surface IgM-mediated apoptosis in an anti-IgM resistant variant of WEHI-231 lymphoma cells by HS1,a protein tyrosine kinase substrate." Proc.Natl.Acad.Sci.USA. 92. 7302-7306 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishizumi H.: "Impaired proliferation of peripheral B cells and indication of autoimmune disease in lym-deficient mice." Immunity. 3. 549-560 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsushita S.: "Allele specificity of structural requirement for peptides bound to HLA-DRB1^*040 and-DRB1^*0406 complexes:Implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome." J.Exp.Med.180. 873-883 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Seino K., et al.: "Anti-tumor effect of locally produced Fas ligand." Nature Medicine. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaneko Y., et al.: "CD40-mediated stimulation of B1 and B2 cells : implication in autoantibody production in murine lupus" Eur.J.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato K., et al.: "Local production of IL-12 p40 suppresses Th1-mediated immune responses and prevents allogeneic myoblast rejection." Proc.Natl.Acad.Sci, USA. 93. 9085-9089 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida T., et al.: "Defective B-1 cell development and impaired immunity against angiostronglylus cantonensis in IL-5R deficient mice." Immunity. 4. 483-494 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kayagaki N., et al.: "Metalloproteinase-mediated release of human Fas ligand." J.Exp.Med.182. 1777-1783 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] KiKuchi Y., et al.: "Cd38 ligation induced Btk activation and enhanced expression of IL-5 receptor a chain." Proc.Natl.Acad.Sci.USA. 92. 10879-10883 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda T., et al.: "Restoration of surface IgM-mediated apoptosis in an anti-IgM resistant variant of WEHI-231 lymphoma cells by HS1, a protein tyrosine kinase substrate." Proc.Natl.Acad.Sci.USA. 92. 7302-7306 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishizumi H., et al.: "Impaired proliferation of peripheral B cells and indication of autoimmune disease in lym-deficient mice." Immunity. 3. 549-560 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsushita S., et al.: "Allele specificity of structural requirement for peptides bound to HLA-DRB1^<**>040 and -DRB1^<**>0406 complexes : Implication for the HLA-associated susceptibility to methimazole-induced-insulin autoimmune syndrome." J.Exp.Med.180. 873-883 (1994)

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

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Published: 1999-03-09  

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