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Experimental study of pathogenesis and therapeutic effect for Sjogren's syndrome

Research Project

Project/Area Number 05557079
Research Category

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

Allocation TypeSingle-year Grants
Research Field Morphological basic dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

HAYASHI Yoshio  Department of Pathology, School of Dentistry, The University of Tokushima, Professor, 歯学部, 教授 (00127854)

Co-Investigator(Kenkyū-buntansha) HAMANO Hironori  Department of Pathology, School of Dentistry, The University of Tokushima, Resea, 歯学部, 助手 (10238074)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1994: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1993: ¥9,000,000 (Direct Cost: ¥9,000,000)
KeywordsSjogren's syndrome / Animal model / T cell receptor / Cytokine / MRL / lpr mice / NFS / sld mice / Autommunity / RT-PCR / lprマウス / シェーグレン症候群 / SCIDマウス
Research Abstract

We have established a new animal model for human primary Sjogren's syndrome in NFS/sld mutant mice bearing autosomal recessive gene with sublingual gland differentiation arrest. Significant inflammatory changes develop spontaneously in both the salivary and lacrimal glands of NFS/sld mutant mice thymetomized 3 days after birth without later immunization, whereas no inflammatory lesions were found in other organ in general. This pathology resembles primary Sjogren's syndrome involving the parotid, submandibular salivary gland and lacrimal gland. A significantly higher incidence of autoimmune lesions in females was found, and the antisalivary duct anibody was frequently detected in sera from mice with autommune lesions, but not in control mice. The inflammatory infiltrates in the salivary and lacrimal glands consisted mainly of CD3^+, CD4^+ T cells with lesser proportion of CD8^+ T cells, and B220^+ B cells. Mac-1^+ cells were occasionally found within these lesions. When the repertoire of T cell receptor (TCR) Vbeta genes transcribed and expressed within the inflammatory infiltration was analyzed in mice with autommune lesions, a preferential utilization of TCR Vbeta gene (vbeta8>Vbeta6) was detected in these lesions during the course of disease. Moreover, we succeeded in adoptive transfer of Sjogren's syndrome in MRL/lpr mice into SCID mice by intraperioneal injection using the salivary gland inflammatory cells. The treament with anti-CD4 and anti-Vbeta8 prevented the adoptive transfer into SCID mice. We concluded that murine autoimmune lesions developping in the salivary and lacrimal glands are obvious to depend on T-cell dependent immune response, and therapies designed with similar approaches might be used to prevent autoimmune diseases.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Hironori Hamano et al.: "Expression of cytokine genes during development of autoimmune sialadenitis in MRL/1pr mice" European Journal of Immunology. 23. 2387-2391 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshio Hayashi et al.: "Pathogenesis of Sjogren-syndrome-like autoimmune lesions in MRL/1pr mice" Pathology International. 44. 559-568 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshi Hayashi et al.: "Transfer of Sjogren-like autoimmune lesions in SCID mice and its prevention by anti-CD4 and TCRVb treatment" Sjogren's syndrome.State of the art. 47-51 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Norio Haneji et al.: "A new animal model for primary Sjogren's syndrome in NFS/sld mutant mice" Journal of Immunology. 153. 2769-2777 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshi Hayashi et al.: "Transfer of Sjogren's syndrome-like autoimmune lesions and prevention oflesions by anti CD4 and anti T cell receptor Vb treatment" European Journal of Immunology. 24. 2826-2831 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Maki Moritani et al.: "Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes in non-obese diabetic mice" International Immunology. 6. 1927-1936 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hamano, H et al: "Expression of cylokine genes during development of autoimmune sialadenitis in MRL/lpr mice" Eur.J.Immunol. 23. 2387-2391 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hayashi, Y et al: "Pathogenesis of Sjogren's syndrome-like autoimmune lesions in MRL/lpr mice" Pathol.Int.44. 559-568 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Haneji, H et al.: "A new animal model for Sjogren's syndrome in NFS/sld mutant mice" J.Immunol. 153. 2769-2777 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hayashi, Y et al.: "Transfer of Sjogren's syndrome-like autoimmune lesions into SCID mice and prevention of lesions by anti-CD4 and anti-T cell receptor antibody treatment" Eur.J.Immunol. 24. 2826-2831 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hayashi, Y et al.: "Biased T cell receptor Vbeta gene usage during development of Sjogren's syndrome in MRL/lpr mice depending on the stage of the disease" Arthritis Rheum. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hironori Hamano et al: "Expresion of cytokine genes during development of autoimmune sialadenitis in MRL/lpr mice" European Journal of Immunology. 23. 2387-2391 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshio Hayashi et al: "Pathogenesis of Sjogren′s syndrome-like autoimmune lesions in MRL/lpr mice" Pathology International. 44. 559-568 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshio Hayashi et al: "Transfer of Sjogren-like autoimmune lesion in SCID mice and its prevention by anti-CD4 and TCRVb treatment" Sjogren′s syndrome.State of the art. 47-51 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Norio Haneji et al: "A new animal model for primary sjogren′s syndrome in NFS/sld mutant mice" Journal of Immunology. 153. 2769-2777 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshio Hayashi et al: "Transfer of Sjogren′s syndrome-like autoimmune lesions into SCID mice and prevention of lesions by anti-CD4" European Journal of Immunology. 24. 2826-2831 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Maki Moritani et al: "Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes" International Immunology. 6. 1927-1936 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hironori Hamano: "Expression of cytokine genes on development of autoimmune sialadenitis in MRL/lpr mice" Eur.J.Immunol.23. 2387-2391 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshio Hayashi: "Pathogenesis of Sjogren's syndrome-like autoimmune lesion in MRL/lpr ice" Pathol.International. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshio Hayashi: "Transfer of murine Sjogren-like autoimmune lesions into SCID mice and its prevention by anti-CD4 and TCR Vβ8 treatment" Proc.4th Int.Sjogren's Synd.Sympo.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 林 良夫: "シェーグレン症候群の病因解析" 最新医学. 49(1). 151-156 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 林 良夫: "自己免疫疾患の発症機構におけるT細胞の役割" 臨床免疫. (印刷中). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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