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Mechanism for MHC class II E region-linked autoimmune suppression.

Research Project

Project/Area Number 12670309
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionJUNTENDO UNIVERSITY

Principal Investigator

HIROSE Sachiko  Juntendo Univ., Dept. Pathol., Associate Proffessor, 医学部, 助教授 (00127127)

Co-Investigator(Kenkyū-buntansha) ZHANG Danqing  Juntendo Univ., Dept. Pathol., Instructor, 医学部, 助手 (40296877)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordssystemic lupus erythematosus / MHC class II / I-A molecule / I-E molecule / H-2 recombination / H-2-congenic mouse / suppressor T cells / MHC class II / H-2 recombination / H-2-congeuicマウス / ヘテロ接合性
Research Abstract

The (NZB x NZW) F1 mice spontaneously develop autoimmune disease resembling human systemic lupus erythematosus. The occurrence of disease is restricted by H-2^<d/z> heterozygosity of the major histocompatibility complex (MHG), H-2^<d> from NZB and H-2^<Z> of NZW strains. Studies on autoreactive T cell clones suggest that Aα^<d> Aβ^<z> molecules may be candidate for disease acceleration. In the present studies, we established H-2-congenic NZB.GD and NZW.GD strains carrying H-2^<g2> haplotype, showing the intra-H-2 recombination between H-2^d and H-2^b haplotype, as a result of crossing-over which occurred to the left of the Ea subregion. Because Ea^b is a null allele, these congenic strains do not express E molecules. Comparison of disease severity among (NZB x NZW.H-2^d) Fl, (NZB x NZW.GD) F1 and (NZB.GD x NZW.GD) Fl mice showed that disease severity is controlled by Ea-linked subregion and that Ea^d suppress the disease. Furthermore, the disease severity in (NZB x NZW. GD) F1 mice transferred with CD^<8+> T cells from (NZB x NZW.H-2^<d>) F1 mice was markedly suppressed, as compared with non-treated (NZB x NZW.GD) F1 mice. To identify exact subregion for disease suppression, we have been establishing new H-2 recombinant-congenic strains carrying intra-H-2 recombination between H-2^<d> and H-2^<b> haplotype to the right of Ea subregion. The mechanism for disease suppression by CD8^+ T cells is under investigation.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Ochiai, K. et al.: "Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice"Int.Immunol. 12. 1-8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakajima, A. et al.: "Treatment of lupus in NZB/W Fl mice with monoclonal antibody against Fas ligand"J.Autoimmunity. 14. 151-157 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jiang, Y. et al.: "Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility"Immunogenetics. 51. 429-435 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hrose, S. et al.: "Genetic aspects of inherent. B-cell abnormalities associated with SLE and B-cell malignancy : Lessons from New Zealand mouse models"Int Rev.lmmunol. 19. 389-421 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jiang, Y. et al.: "Polymorphism and chromosomal mapping of the murine gene for B cell activating factor belonging to the TNF family (BAFF) and association with the autoimmune phenotype"Immunogenetics. 53. 810-813 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hirose, S. et al.: "Genetic basis of systemic lupus erythematosus"Drug of Today, Prous Science, Barcelona, Spain. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hamani, Y., Hirose, S.: "Microsatellite method.In Laboratory Techniques in Renal Cell and Molecular Biology"KARGER. 209(156-161) (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ochiai, K.et al.: "Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice."Int. Immunol.. 12. 1-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakajima, A.et al: "Treatment of lupus in NZB/W F1 mice with monoclonal antibody against Fas ligand."J. Autoimmunity. 14. 151-157 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jiang, Y.et al.: "Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility."Immunogenetics. 51. 429-435 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shirai.T., et al.: "Genetics of SLE : a sine qua non for identification"Int Rev. Immunol.. 19. 289-295 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hirose, S.et al.: "Genetic aspects of inherent B-cell abnormalities associated with SLE and B-cell malignancy : Lessons from New Zealand mouse models."Int Rev. Immunol.. 19. 389-421 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hamano, Y.&Hirose, S.KARGER: "Microsatellite method."In Laboratory Techniques in Renal Cell and Molecular Biology. KARGER,. 156-161 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jiang, Y., et al.: "Polymorphism and chromosomal mapping of the murine gene for B Cell activating factor belonging to the TNF family(BAFF) and association with the autoimmune phenotype."Immunogenetics. 53. 810-813 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shirai, T., et al.: "Genome screening for susceptibility loci in systemic lupus erythematosus."Am. J. Pharmacogenomics. 2. 1-12 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hirose, S., et al.: "Genetic basis of systemic lupus erythematosus."Drug of Today, Prous Science, Barcelona, Spain. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takasaki, Y., et al.: "Reactivity of anti-PCNA murine monoclonal antibodies and human autoantibodies to the PCNA multiprotein complexes involved in cell proliferation"J. Immunol.. 166. 4780-4787 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shike, T., et al.: "Susceptibility and negative epistatic loci contributing to type 2 diabetes mellitus and related phenotypes in a KK/Ta mouse model"Diabetes. 50. 1943-1948 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirose, S., et al.: "Genetic study of SLE : lessons from mouse models"Mod. Rheumatol.. 11. 262-262 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jiang, Y., et al.: "Polymorphism and chromosomal mapping of the murine gene for B cell activating factor belonging to the TNF family (BAFF) and association with the autoimmune phenotype"Immunogenetics. 53. 810-813 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirose, S., et al.: "Genetic basis of systemic lupus erythematosus"Drug of Today, Prous Science, Barcelona, Spain. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shirai, T., et al: "Genome screening for susceptibility loci in systemic lupus erythematosus"Am. J. Pharmacogenomics. 2. 1-12 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ochiai,K. et al.: "Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice."Int.Immunol.. 12. 1-8 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakajima,A. et al.: "Treatment of lupus in NZB/W F1 mice with monoclonal antibody against Fas ligand."J.Autoimmunity. 14. 151-157 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jiang,Y. et al.: "Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility."Immunogenetics. 51. 429-435 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirose,S. et al.: "Genetic aspects of inherent B-cell abnormalities associated with SLE and B-cell' malignancy : Lessons from New Zealand mouse models."Int Rev.Immunol.. 19. 389-421 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shirai,T.& Hirose,S.: "Genetics of SLE ; A sine qua non for identification."Int Rev.Immunol.. 19. 289-295 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hida,S. et al.: "CD8^+ T cell-mediated transcriptional attenuator of interferon-α/β signaling."Immunity. 13. 643-655 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hamano,Y.& Hirose,S.: "Microsatellite method.In Laboratory Techniques in Renal Cell and Molecular Biology."KARGER. (209)(156-161) (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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