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Pathogenic Role of T Cell Mediated Cytotoxicity on Fibroblasts in Dermatomyositis

Research Project

Project/Area Number 63570303
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionToho University

Principal Investigator

SAITO Eizou  Toho University, School of Medicine Assist. Prof., 医学部, 助教授 (10112690)

Co-Investigator(Kenkyū-buntansha) ARAKI Hiroshi  Toho University, School of Medicine, Resident, 医学部, 助手 (80120228)
Project Period (FY) 1988 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Keywordsdermatomyositis / polymyositis / fibroblast / mononuclear cell / cytotoxic T lymphocyte / cytokinesis / glucocorticoid / malignancy / サイトカン / 病因 / 自己免疫 / 結合繊 / 単球 / 間質
Research Abstract

Head Investigator : #493610112690, Eizo Saito, Toho Uninv., Department of Medicine, Assistant Professor
Investigator : #471180120228, Hiroshi Araki, Toho Uninv., Department of Medicine, Assistant
The effect of peripheral mononuclear cells (MNC) from patients with dermatomyositis (DM) on cultured human skin fibroblasts was studied and the following results were obtained ; (1) When human skin fibroblasts were incubated with DM MNC, striking attachment of MNC around fibroblasts was observed. Cell proliferation of fibroblasts after incubation was significantly deppressed. ^<51>Cr releasing study demonstrated that DM MNC possess dominant cytotoxic activity on fibroblasts. (2) The damaging effects of DM MNC were specific to fibroblasts. It was also specific to DM MNC, and MNC from other subjects including polymyositis patients did not show such effect. (3) Effector cells were T8 positive lymphocytes. The presence of monocytes was essential. (4) Attachment of MNC to fibroblasts was an important … More step. (5) When DM lymphocytes and normal monocytes were added to fibroblasts, the cytotoxicity was observed, whereas no cytotoxicity was observed when normal lymphocytes and DM monocytes were added. (6) The cytotoxicity was inhibited by anti-IL-2 antibody, but not by anti-IL-1 and anti-IL-6 antibodies. In the presence of the conditioned medium obtained from DM MNC culture, normal MNC showed the cytotoxicity on fibroblasts. When normal MNC were stimulated with IL-2, these cells also gained cytotoxic activity on autologous and allogenic fibroblasts. Consequently, IL-2 seems to play an important role. (7) Glucocorticoids inhibited the cytotoxicity in a dose-response manner. (8) MNC from DM patients with malignancy showed the cytotoxicity on fibrlblasts. It was completely lost after treatment and the malignancy resolved. Contrarily, MNC from uncomplicated DM patients continued to show cytotoxicity even when they were in inactive stage. Then, in patients with DM and malignancy, the primary lesion seems to be malignancy. Results of the present study strongly suggest that DM is a disease which is mediated by the autoimmune cytotoxic T lymphocyte reaction against interstitial tissues. Less

Report

(4 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Eizo Saito: "Mechanism of damaging effect of dermatomyositis mononuclear cells on cultured human skin fibroblasts" J Rheumatol. 16. 1055-1060 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Eizo Saito: "Etialogical difference between polymyositis and dermatomyositis" Jpn J Rheumatol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Eizo Saito: "Possible pathogenic role of T cell mediated cytotoxicity on fibroblasts in dermatomyositis associated malignant neoplasms" Ann Rheum Dis.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Eizo Saito, Kyoko Kuroda, Yukiko Yoshimoto, Hisaji Oshima, Masao Kinoshita: "Mechanism of damaging effect of dermatomyositis mononuclear cells on cultured human skin fibroblasts." J Rheumatol. 16. 1055-1060 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Eizo Saito, Kyoko Murabayashi, Hitomi Yoshida, Satoshi Okada, Masao Kinoshita: "Etiological difference between polymyositis and dermatomyositis." Jpn J Rheumatol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Eizo Saito, Satoshi Okada, Kyoko Murabayashi, Takehiko Ogawa, Hitomi Yoshida, Masao Kinoshita: "Possible pathogenic role of T cell mediated cytotoxicity on fibroblasts in dermatomyositis associated with malignant neoplasms" Ann Rheum Dis.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Eizo Saito,Kyoko Murabayashi,Hitomi Yosida,Satoshi Okada,Masao Kinoshita: "Etiological Difference between polymyositis and dermetomyositis" Jpn J Rheumatol.

    • Related Report
      1990 Annual Research Report
  • [Publications] Satoshi Okada,Eizo Saito,Hisaji Oshima,Masao Kinoshita: "Autoantibody to grouth homone in a patient with myasthenia gravis" J Endocrinol. 127. 533-538 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Eizo Saito,Satoshi Okada,Kyoko Murabayashi,Takehiko Ogawa,Hitomi Yoshida,Masao Kinoshita: "Possible Pathogenic role of T cell mediated cytotoxicity on fibroblasts in dertomyositis associated with malignant neoplasms" Ann Rheum Dis.

    • Related Report
      1990 Annual Research Report
  • [Publications] Eizo Saito: "Mechanism of damaging effect of devmatomyositis monoluclear cells on culured human skin fibroblasts" J Rheumatol. 16. 1055-1060 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Eizo Saito: "Fluorescent antibodies in polymyositis using wltured human skin fibvobasts gaunlar perimuclear ytolasm staining patter by seva from patients with polymyositis and pulmonary fibvosis" J Rheumatol. 16. 47-54 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Eizo Saito: "Damaging effet of peripheral alls of dermatonyositis on cuteired human skin fibroblasts" J Rheumatol. 14. 936-941 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] Eizo Saito: "Large molewlew weiget ACTH immunoactioity in a patient with adrenoleukomycloneuropathy" An J Med. 83. 777-782 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] Hitomi Yoshida: "Hypevparathyoidism in patients with myotonic dystropky" J clin Endocrinol Metaf. 67. 488-492 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] 斉藤栄造: "膠原病-進歩と問題点、病型診断の可能性とその臨床的意義多発性筋炎・皮膚筋炎" 最新醫学. 45. 334-341 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] 塩川優一責任監修: "リウマチ学" 同之書院, 1429 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 柏崎禎夫編集: "チャ-ト式抗炎症剤使用ハンドブック" メディカルレビュ-社,

    • Related Report
      1989 Annual Research Report
  • [Publications] Eizo Saito: J Rheumatol. 14. 936-941 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Eizo Saito: J Rheumatol. 16. 47-54 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Eizo Saito: J Rheumatol. 1989.

    • Related Report
      1988 Annual Research Report
  • [Publications] 斉藤栄造: Mebio. 4. 82-86 (1987)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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