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Study of the pathogenesis of intrinsic asthma by establishing T cell clones

Research Project

Project/Area Number 04454250
Research Category

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

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionUniversity of Tokyo

Principal Investigator

ITO Koji  University of Tokyo, Faculty of Medicine, professor, 医学部(病), 教授 (10008310)

Co-Investigator(Kenkyū-buntansha) MORITA Yutaka  Univ. of Tokyo, Faculty of Medicine, associate prof., 医学部(病), 助教授 (60107620)
TAKIZAWA Hajime  Univ. of Tokyo, Faculty of Medicine, assistant prof., 医学部(病), 助手 (80171578)
MORI Akio  Univ. of Tokyo, Faculty of Medicine, assistant professor, 医学部(病), 助手 (80251247)
SUKO Mastunobu  Univ. of Tokyo, Faculty of Medicine, lecturer, 医学部(病), 講師 (80107622)
OKUDAIRA Hirokazu  Univ. of Tokyo, Faculty of Medicine, lecturer, 医学部(病), 講師 (30106645)
高石 敏昭  東京大学, 医学部(病), 助手 (40154736)
平井 浩一  東京大学, 医学部(病), 助手 (10156630)
灰田 美知子  東京大学, 医学部(病)物療内科, 医員 (90240712)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1992: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsBronchial asthma / T cell / eosinophil / Interleukin-5 / T cell clone / アレルギー / インターロイキン5 / T cell clone / アレルゲン / Der f II / T cell / ハウスダストマイト
Research Abstract

Chronic eosinophilic inflammation of bronchial mucosa has been recognized in the pathophysilology of bronchial asthma. The roles of T cells and T cell cytokines, including especially IL-5, have been strongly implicated in the local infiltration and activation of eosinophils. We have indicated that enhanced IL-5 production by CD4^+ T cells is observed in both atopic and non-atopic (intrinsic) asthmatics. Control of IL-5 production by activated T cells must be a beneficial approach to manage allergic diseases characterized by eosinophilic inflammation. In order to delineate the precise mechanisms of IL-5 production by human "allergic" T cells, we established T cell clones from asthmatic patitents and analyzed cytokine production by those helper T cell clones. Both PKC activation and Ca^<++> influx were required for IL-5 synthesis. The transcription factors, NF-AT and AP-1 were suggested to be involved in IL-5 gene transcription. IL-5 synthesis by human T cells was dependent on endogeneously produced IL-2. Human recombinant IL-2 initiated IL-5 gene transcription in IL-5 producing T cell clones. PBMC of some intrinsic asthmatics produced IL-5 in response to mite allergen extract. T cell clones established from such patients did produce IL-5 in response to mite allergen, suggesting that mite allergen might be in part responsible for so called "intrinsic" asthma.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Mori,A.,Suko,M.,et al.: "Regulation of Interleukin-5 production by peripheral blood mononuclear cells from atopic patients with FK506,Cyclosporin A and Glucocorticoid." Int.Arch.Allergy Immunol.104(S1). 32-35 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori,A.,Suko,M.,et al.: "Atopic diseases and eosinophilic inflammation-possible management with agents which downregulate IL-5 gene transcription." Environ.Dermatol.1. 42-54 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori,A.,Suko,M.,et al.: "Interleukin-5 production by CD4^+ T cells of as thmatic patients is suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosporin A.21GC03:Int.Immunol." 7(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori,A.,Suko,M.,et al.: "Allergen-specific human T cell clones produce IL-5 upon stimulation with Th1 cytokine,IL-2." Int.Arch.Allergy Immunol.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori,A.,Suko,M.,et al.: "Analysis of human IL-5 gene transcription by T cell clones and hybridomas." Int.Arch.Allergy Immunol.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Okudaira,H.,et al.: "Enhanced production and gene expression of IL-5 in bronchial asthma-management of atopic diseases with agents that downregulate IL-5 gene transcription." A.C.I.News. 6. 19-25 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 森 晶夫、奥平博一: "喘息の基礎から臨床まで(伊藤幸治編)" 医薬ジャーナル社(in press), (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 森 晶夫、伊藤幸治: "アレルギー性炎症(牧野荘平編)" メディカルレビュー社, 215 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori, A., Suko, M., et al.: "Regulation of Interleukin-5 production by peripheral blood mononuclear cells from atpic patiens with FK506, cyclosporin A and Glucocorticoid." Int. Arch. Allergy Immunol.104 (S1). 32-35 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori, A., Suko, M., et al.: "Atopic diseases and eosinophilic inflammation-possible management with agents which downregulate IL-5 gene transcription." Environ. Dermatol.1. 42-54 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori, A., Suko, M., et al.: "Interleukin-5 production by CD4^+ T cells of asthmatic patients in suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosproin A." Int. Immunol.7(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] Mori, A., Suko, M., et al.: "Allergen-specific human T cell clones produce IL-5 upon stimulation with Th1 cytokine, IL-2." Int. Arch. Allergy Immunol.(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] Mori, A., Suko, M., et al.: "Analysis of human IL-5 gene transcription by T cell clones and hybridomas." Int. Arch. Allergy Immunol.(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] Okudaira, H., et al.: "Enhanced production and gene expression of IL-5 in bronchial asthma-management of atopic diseases with agents that downregulate IL-5 gene transcription." A.C.I.News. 6. 19-25 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori, A.and Okudaira, H.: "Cytokine production in asthma." Asthma : basic to clinic (edit. Prof. K.Ito) Iyaku-journal Ltd. (Tokyo). (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] Mori, A.and Ito, K.: "Cytokines involved in asthma." Allergic inflammation (edit. Prof. S.Makino) Medical Review Ltd. (Tokyo). 63. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mori,A.,Suko,M.,et al.: "Regulation of Interleukin-5 production by peripheral blood mononuclear cells from atopic patients with FK506,Cyclosporin A and Glucocorticoid." Int.Arch.Allergy Immunol.104(S1). 32-35 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mori,A.,Suko,M.,et al.: "Atopic diseases and eosinophilic inflammation-possible management with agents which downregurate IL-5 gene transcription." Environ.Dermatol.1. 42-54 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mori,A.,Suko,M.,et al.: "Interleukin-5 production by CD4^+ T cells of asthmatic patients is suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosporin A." Int.Immunol.7(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mori,A.,Suko,M.,et al.: "Allergen-specific human T cell clones produce IL-5 upon stimulation with Th1 cytokine,IL-2." Int.Arch.Allergy Immunol.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mori,A.,Suko,M.,et al.: "Analysis of human IL-5 gene transcription by T cell clones and hybridomas." Int.Arch.Allergy Immunol.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okudaira,H.,et al.: "Enhanced production and gene expression of IL-5 in bronchial asthma-management of atopic diseases with agents that downregulate IL-5 gene transcription." A.C.I.News. 6. 19-25 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 森 晶夫、奥平博一: "喘息の基礎から臨床まで(伊藤幸治編)" 医薬ジャーナル社(in press), (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 森 晶夫、伊藤幸治: "アレルギー性炎症(牧野荘平編)" メディカルレビュー社, 215 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] A.Mori,M.Suko,et al.: "Regulation of Interleukin-5 production by peripheral blood mononuclear cells from atopic patients with FK506,cyclosproin A and glucocorcicoid." Int.Arch.Allergy Immnol.S1(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 森晶夫、須甲松伸、他: "気管支喘息患者末梢リンパ球におけるIL-5産生の解析" Proc.Jpn.Soc.Immunol.23. 499 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 森晶夫、須甲松伸、他: "アレルゲン特異的ヒトT細胞クローンを用いたインターロイキン産生調節の検討" Jpn.J.Allergol.42. 1334 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 西崎陽子、森晶夫、他: "気管支喘息患者末梢リンパ球のダニアレルゲン反応性の検討" Jpn.J.Allergol.42. 1348 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高橋靖江、森晶夫、他: "アトピー型、非アトピー型気管支喘息におけるT細胞反応性の比較" Jpn.J.Allergol.42. 1335 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 森晶夫、須甲松伸、他: "ロキシスロマイシンおよびエリスロマイシンの気管支喘息患者末梢血単核球IL-5産生能におよぼす影響" Jpn.J.Allergol.42. 424 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 森晶夫、伊藤幸治: "アレルギー性炎症" メディカルレビュー社(東京), 215 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akio Mori 7: "Interleukin-4 gene expression in high and low IgE responder mice." Int.Arch.Allergy Appl.Immunol.92. 100-102 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hirokazu Okudaira 7: "T cell dependent accumulation of eosinophils in the lung and its inhibition by monoclonal anti-Interleukin 5." Int.Arch.Allergy Appl.Immunol.94. 171-173 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akio Mori 5: "Interleukin-4 gene expression in human peripheral blood mononuclear cells." Int.Arch.Allergy Appl.Immunol. 95. 282-284 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tohru Ando 11: "Is a trypsin-like protease of mites a Der f 3 allergen?" Jpn.J.Allergol.41. 704-707 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Go Matsuzaki 6: "Anti-Der f 1 and anti-Der f II IgE antibodies in atopic patients." Int.Arch.Allergy Appl.Immunol.

    • Related Report
      1992 Annual Research Report
  • [Publications] Mamoru Ito 7: "Regulation of human IgE production by peripheral blood mononuclear cells (PBMC) from atopic patients in mice with severe combined immunodeficiency." Int.Arch.Allergy Appl.Immunol.

    • Related Report
      1992 Annual Research Report
  • [Publications] Hirokazu Okudaira: "Dust Mite Allergens and Asthma" Mosby-Year Book,Inc., 1046 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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