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Induction of vasculitis by vascular smooth muscle-specifc T cells and analysis of its mechanism

Research Project

Project/Area Number 06807020
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

OZAKI Shoichi  Department of Medicine and Clinical Science, Kyoto University Associate Professor, 医学研究科, 講師 (00231233)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsvasculitis / animal model / vascular smooth muscle / MRL-+ / + mouse / CD4^+ T cells / pulmonary vasculitis / cytotoxicity / Fas ligand / MRL / nマウス
Research Abstract

We established a T-cell line, MV1, specific for rat vascular smooth muscle antigen from the regional lymph nodes of immunized MRL/Mp-+/+ mice. Adoptive transfer of MV1 T cells induced vasculitis lesions in the lungs of the syngeneic recipient mice pre-treated with cyclophosphamide. Flow cytometric analysis showed that MV1 was a CD4+ T cell line. The T cells proliferated in the presence of the vascular smooth muscle antigen and mitomycin C-treated syngeneic spleen cells. The cross experiments using an ovalbumin-specific T-cell line demonstrated that MV1 was specific for vascular smooth muscle antigen. The antigen-specific proliferation of MV1 was CD4 dependent, which was consistent with the flow cytometric analysis. In addition, MV1 T cells, upon activation with anti-CD3 antibody or antigen-specific activation, killed A 20.2J mouse B lymphoma cells. MV1 T cells also killed a CD95 (Fas) -transfected T lymphoma line, but not its parental Fas-negative cell line. These findings indicated that MV1 T cells killed target cells via a Fas ligand (FasL) /Fas pathway. The cytotoxicity of MV1 T cells may play an important role in the development of the vasculitis in this model. Although the antigenic epitopes of MV1 and the lung specificity of the vasculitis remain to be clarified, MV1-induced vasculitis should serve as an experimental model of human pulmonary vasculitis.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Suda T., 他: "Expression of the Fas ligand in cells of T-cell-lineage." J. Immunl.154. 3806-3813 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ozaki S., 他: "Biological response modifier(BRM)as an antigen IV. T-cell lines specific for BRM kill tumor cells in a BRM-specific manner." Cancer Immunol. Immunother.40. 219-227 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takahashi C., 他: "Portal hypertension associated with anticardiolopin antibodies in a case of systemic lupus erythematosus." Lupus. 4. 232-235 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mori K., 他: "Gene expression of the human prostaglandin Ereceptor EP4 subtype: differential regulation in monocytoid and lymphoid lineage cells phorbor ester." J. Mol. Med.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sumita.S., 他: "A vascular smooth muscle-specific CD4T-cell line that induces pulmonary vasculitis in MRL_<-+>/_+mice." Clin. Fxp. Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 尾崎承一: "BRM特異的CD4T細胞の細胞障害機序-Fasリカンド/Fasを介したアポトーシス。" Biotherapy Today. 2. 99-103 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 露岡令子、他(共著): "免疫疾患-state of arts-" 今西二郎、他 (編)・医歯薬出版(東京), 473 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 尾崎承一(共著): "内科学" 小俣政男、他(編)・医学書院(東京)(印刷中),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suda T., et al.: "Expression of the Fas ligand in cells of T-cell-lineage." J.Immunol.154. 3806-3813 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ozaki S., et al.: "Biological response modifier (BRM) as an antigen. IV.T-cell lines specific for BRM kill tumor cells in a BRM-specific manner." Cancer Immunol.Immunother.40. 219-227 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takahashi C., et al.: "Portal hypertension associated with anticardiolipin antibodies in a case of systemic lupus erythematosus." Lupus. 4. 232-235 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mori K., et al.: "Gene expression of the human prostaglandin E receptor EP4 subtype : differential regulation in monocytoid and lymphoid lineage cells by phorbor ester." J.Mol.Med.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sumita S., et al.: "A vascular smooth muscle-specific CD4 T-cell line that induces pulmonary vasculitis in MRL-+/+ mice." Clin.Exp.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shoichi Ozaki: "Mechanism of cytotoxicity by BRM-specific CD4 T cells : apoptosis via Fas ligand/Fas pathway" Biotherapy Today. 2. 99-103 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuyuoka R., et al. (co-authors): "Immunological Diseases-State of Arts" Imanishi J., et al.eds.Ishiyaku Shuppan, Tokyo. 473 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ozaki S., et al. (co-authors): "Naikagaku (Internal Medicine)" Omuta M., et al.eds. Igaku shoin, Tokyo. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suda. T.,他: "Expression of the Fas ligand in cells of T-cell-lineage." J. Immunol.154. 3806-3813 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ozaki. S.,他: "Biological response modifier (BRM)as an antigen. IV. T-cell lines specific for BRM kill tumor cells in a BRM-specific manner." Cancer Immunol. Immunother.40. 219-227 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takashi. C.,他: "Portal hypertension associated with anticardiolipin antibodies in a case of systemic lupus erythematosus." Lupus. 4. 232-235 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mori K.,他: "Gene expression of the human prostaglandin E receptor EP4 subtype: differential regulation in monocytoid and lymphoid lineage cells by phorbor ester." J. Mol. Med.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Sumita S.,他: "A vascular smooth muscle-specific CD4 T-cell line that induces pulmonary vasculitis in MRL-^+/^+mice." Clin. Exp. Immunol.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] 尾崎承一: "BRM特異的CD4T細胞の細胞障害機序-Fasリガンド/Fasを介したアポトーシス。" Biotherapy Today. 2. 66-103 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 露岡令子、他(共著): "免疫疾患-state of arts" 今西二郎、他(編)・医歯薬出版(東京), 473 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 尾崎承一(共著): "内科学" 小俣政男、他(編)・医学書院(東京)(印刷中),

    • Related Report
      1995 Annual Research Report
  • [Publications] Okazaki T.,他: "CD4^+ T cells require adhesion via LFA-1/ICAM-1 to induce target apoptosis in TNF-independent pathway." Cell.Immunol.156. 135-145 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Okazaki S.,他: "Biological response modifier (BRM) as an antigen.III.T-cell lines specific for BRM kill tumor cells in a BRM-specific manner." Cancer Immunol.Immunother.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Suda T.,他: "Expression of the Fas ligand in cells of T-cell-lineage." J.Immunol.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] 尾崎承一・他: "T細胞ワクシネーション・ペプチド療法" 内科. 73. 715-717 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 大村浩一郎・他: "膠原病に対する特殊免疫学的治療" 総合臨床. 43. 1098-1101 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 尾崎承一: "自己免疫疾患-T細胞レセプター" Biotherapy. 8. 818-825 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ozaki S.(共著): "Cellular Immunology Labfax" Delves P.J.・編 BIOS Scientific Publishers(Oxford), 259 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 尾崎承一(共著): "NEWメディカルサイエンス:自己免疫疾患" 山本一彦・編 羊土社(東京), 172 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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