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Analysis of multiple organ-localized autoimmune diseases in nude mice grafted with rat thymic rudiment

Research Project

Project/Area Number 61570187
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionAichi Cancer Center

Principal Investigator

TAGUCHI Osamu  Laboratory of Experimental Pathology, 病理学第二部, 主任研究員 (00142167)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Toshitada  Laboratory of Immunology, 免疫学部, 部長 (00124529)
Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsThymus / Organ-localized autoimmune disease / Nude mouse / Thyroiditis / Gastritis / 卵巣炎 / L3T4抗原 / 臓器局在性自己免疫病 / 唾液腺炎
Research Abstract

The most important function of the thymus is education of T cells which properly recognize self and non-self.The basis of this function is thought to link to harmonious interaction between the thymic epithelial cells and T cell precursors.Pathogenesis of autoimmune disease has not been established so for. Recently we developed a model of multiple organ-localized autoimmune diseases probably based on abnormal or incomplete cell-to-cell interactions in the thymus.
We transplanted thymic rudiments from 15-day-/ld embryonic rats to renal subcapsule of BALB/c nude mice(TG nude)for reconstitution of T cell function. The rudiments developed well and formed a proper thymus structure composed of donor epithelia and host lymphocytes.Examination of antibody responses to SRBC revealed that approximately of half the normal number of indirect PFCs were observed.Skin grafts from syngeneic BALB/c mice and thymic donor rat strains were accepted,whereas those from allogeneic mice and the rats of other than donor strains were vigorously rejected.The TG nude mice survived without any evident infectious diseases umder a conventional environment.Histological and immunofluorescence studies,however,showed a high incidence of multiple organ-localized autoimmune diseases in thyroid,salivary gland,stomach,adrenal,prostate,ovary, and testis in mice that produced the corresponding autoantibodies.
The effector cell popylation in this autoimmune model was studies by adoptive transfer of the lesions into syngeneic BALB/c nu/nu mice.Positive selection experiments by fluorescence-activated cell sorter with monoclonal antibodies were carried out.L3T4 cells,but not LYt-2^+ cells,were capable of inducing lesions. These results together suggested that rat thymic grafts reconstituted T cell functions of nude mice to a considerable degree,but that organ-localized autoimmune diseases developed,probably because certain auto-antigens of the recipients were recognized by the newly reconstituted host immunity.

Report

(3 results)
  • 1987 Annual Research Report   Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] 田口修: The Journal of Experimental Medicine. 164. 60-71 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 田口修: The Journal of Experimental Medicine. 165. 146-156 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 田口修: 医学のあゆみ. 140. 75 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 田口修: 代謝 臨時増刊号「免疫´87」. 24. 75-83 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 田口修: Medical Immunology. 14. 235-239 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 田口修: 臨床免疫. 19. 772-779 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 三宅崇雄: American Journal of Obstetrics and Gynecology. 158. 186-192 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 田口修: "New Horizons in Animal Models for Autoimmune Disease" Academic Press,Inc., 369 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Osamu Taguchi: "Sevelopment of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft" The Journal of Experimental Medicine. 164. 60-71 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Osamu Taguchi: "Self tolerance and localized autoimmunity.Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self tolerance" The Journal of Experimental Medicine. 165. 146-156 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Osamu Taguchi: "Multiple organ-localized autoimmune disease induced by dysfunction of the thymus" Metabolism and Disease(Immunology'87). 24. 75-83 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Osamu Taguchi: "Induction of organ-localized autoimmune diseases by neonatal thymectomy" Medical Immunology. 14. 235-239 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Takao Miyake: "Acute oocytes loss in experimental autoimmune oophoritis as a possible model of premature ovarian failure" American Journal of Obstetrics and Gynecology. 158. 186-192 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Osamu Taguchi: Academic Press, NEW HORIZONS IN ANIMAL MODELS FOR AUTOIMMUNE DISEASE. A novel model of multiple organ-localized autoimmune diseases in nude mice xenografted with thymic rudiment, 331-338 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 田口 修: 代謝臨時増刊号「免疫'87」. 24. 75-83 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 田口 修: Medical Immunology. 14. 235-239 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 田口 修: 臨床免疫. 19. 772-7579 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 池田 洋: The Journal of Immunology.

    • Related Report
      1987 Annual Research Report
  • [Publications] 三宅 崇雄: American Journal of Obstetrics and Gynecology. 158. 186-192 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] 田口 修: "New Horizons in Animal Models for Autoimmune Disease" ACADEMIC PRESS, INC., 369 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 田口修: 164. 60-71 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 田口修: J.Exp.MED.165. 146-156 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 田口修: J.Exp.MED.165. 146-156 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 田口修: 医学のあゆみ. 140. 75 (1987)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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