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Analysis of mechanisms of T cell activation by exotoxins bearing superantigenic properties and induction of abnormal changes by them.

Research Project

Project/Area Number 05454196
Research Category

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

Allocation TypeSingle-year Grants
Research Field Bacteriology (including Mycology)
Research InstitutionTokyo Women's Medical College

Principal Investigator

UCHIYAMA Takehiko  School of Medicine Tokyo Women's Medical College Professor, 医学部, 教授 (00050550)

Co-Investigator(Kenkyū-buntansha) AKIYAMA Toru  School Medicine Instructor, 医学部, 助手 (20246466)
KATO Hidehito  School of Medicine Instructor, 医学部, 助手 (00241084)
YAGI Junji  School of Medicine Assistant Professor, 医学部, 講師 (70182300)
IMANISHI Kenichi  School of Medicine Assistant Professor, 医学部, 講師 (20132920)
厳 小傑  東京女子医科大学, 医学部, 助手 (80195627)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1994: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
Keywordssuperantigen / T cells / MHC class ll molecules / lymphokines / TCR / Vbeta elements / TSS / YPM / Vβエレメント / MHCクラスII / 細菌感染症
Research Abstract

Several of bacterial superantigens are known as pathogenic exotoxins of infectious diseases such as toxic shock syndrome (TSS), scarlet fever and Yersinia pseudotuberculosis infection. These exotoxins, which did not have any apparent cytotoxic activity to various kinds of cells so far invetigated, activate of massive T cell populatious in a TCRVbeta-specific way to produce large amounts of lymhokines. We consider that the overproduction of lymhokines resulting from overactivation of T cells by them are involved primarily in development of abnormal reactions observed in these infectious diseases. We obtained following experimental results during the part two years.
1. We found a novel superantigenic exotoxin (Y.pseudotuberculosis-derived mitogen, YPM) from Y.pseudotuberculosis strains which were isolated from patients with Y.pseudotuberculosis infection. YPM consits of 131 amino acid residues.
2. YPM in a combined injection with D-galactosamine induced lethal shock in C57BL/6 mice in a CD4^+ T cell-dependent way. TNF-alpha seems to be involved in generation of YPM-induced shock.
3. Staphylococcal enterotoxin A (SEA) in a acombined injection with D-galactosamine induced lethal shock in C57BL/6 mice in a CD4^+ T cell-depended way.

Report

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

    (32 results)

All Other

All Publications (32 results)

  • [Publications] 内山竹彦: "Superantigenic properties of a novel mitogenic substance produced by Yersinia pseudotuberculosis isolated from patients manifesting acute and systemic simptoms." J Immunol. 151. 4407 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 高田春比古: "Cytokine induction by extra cellular products of oral viridans Streprococci." Infect.Immun.61. 5252 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 秋山徹: "Purification and partial characterization of product from Yersinia pseudotuberculosis with the ability to activation human T cells." Infect.Immun.61. 3922 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 厳小傑: "Study of activation of murine T cells with bacterial superawtigens in vitro induction of enhanced responses in CD4^+T cells and of anergy in CD8^+T cells" J.Immunol.150. 3873 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 八木淳二: "Stimulator cell type influences the responses of T cells to staphylococcal enterotoxins." J.Immunol.152. 1154 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 八木淳二: "Superantigen-like properties of an antibody bispecific for MHC class II molecules and the VB domain of the T cell antigen receptor." J.Immunol.152. 3833 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 内山竹彦: "A novel superantigenic exotoxin from Yersinia pseadotuberculosis and its position in the classification of the entire bacterial toxins.Contributions to Microbiclogy and lmmunology." S.Karger AG社. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 秋山徹: "Cloning,sequencing and expression of the gene encoding the bacterial Superantigen,Yersinia pseudctuberculosis-derived mitogen(YPM)." J.Immunol.(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takehiko Uchiyama, et al.: "Superantigenic properties of a novel mitogenic substance produced by Yersinia pseudotuberculosis isolated from patients manifesting acute and systemic symptoms." J.Immunol. 151. 4407 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] H.Takada, et al.: "Cytokine induction by extra cellular products of oral viridans Streptococci." Infect.Immun. 61. 3922 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Miyoshi-Akiyama, et al.: "Purification and partial characterization of aproduct from Yersinia pseudotuberculosis with the ability to activate human T cells." Infect.Immun. 61. 3922 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] X-J.Yan, et al.: "Study of activation of murine T cells with bacterial superantigens. In vitro induction of enhanced responses in CD4^+T cells and of anergy in CD8^+T cells." J.Immunol. 150. 3873 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Yagi, et al.: "Stimulator cell type influences the responses of T cells to staphylococcal enterotoxins." J.Immunol. 152. 1154 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Yagi, et al.: "Superantigen-like properties of an antibody bispecific for MHC class II molecules and the Vbeta domain of the T cell antigen receptor." J.Immunol. 152. 3833 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Uchiyama.: "A nobel superantigenic exotoxin from Yersinia pseudotuberculosis and its position in the classification of the entire bacterial toxins. Contributions to Microbiology and Immunology." S.Karger AG lnc. (Printing.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Miyoshi-Akiyama, et al.: "Cloning, sequencing and expression of the gene encoding the bacterial superantigen, Yersinia pseudotuberculosis-derived mitogen (YPM)." J.Immunol. (Printing.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 内山 竹彦: "Superantigthic properties of a novel mitogenic substance prodaced by Yersinia pseudotuberculosis isolated from patients manifesting acute and systemic symptoms." J.Immunol.151. 4407- (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 高田 春比古: "Cytokine induction by extra cellular products of oral viridans Streptococci." Infect.Immun.61. 5252- (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 秋山 徹: "Purification and partial character ization of a product from Yersinia pseudotuberculosis with the ability to activate human T cells." Infect.Immun.61. 3922- (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 厳 小傑: "Study of activation of murine T cells with bacterial superantigens.In vitro induction of enhanced responses in CD4^+T cells and of anergy in CD8^+T cells." J.Immunol.150. 3873- (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 八木 淳二: "Stimulator cell type influences the responses of T cells to staphylococcal enterotoxins." J.Immunol.152. 1154- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 八木 淳二: "Superantigen-like properties of an antibody bispecific for MHC class II molecules and the Vβ domain of the T cell antigen receptor." J.Immunol.152. 3833- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 内山 竹彦: "A ncbel superantigenic exotoxin from Yersinia pseudctuberculosis and its position in the classification of the entire bacterialtoxins.Contributions to Microbiology and Immunology." S.Karger AG 社. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] 秋山 徹: "Cloning,sequencing and expression of the gene encoding the bacterial superantigen,Yersinia pseudctuberculosis-derived mitogen(YPM)." J.Immunol.(印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] X-J.Yan et al.: "Study of activation of murine T cells with bacterial superantigens.In vitro induction of enhanced responses in CD4^+ T cells and of anergy in CD8^+ T cells." J.Immunol.150. 3873-3881 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Miyoshi-Akiyama,et al.: "Purification and partial characterization of a product from Yersinia pseudotuberculosis with the ability to activate human T cells." Infect.Immu.61. 3922-3927 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Uchiyama et al.: "Superantigenic properties of a nobel mitogenic cubstance produced by Yersinia pseudotuberculosis isolated from patients manifesting acute and sysytemic symptoms." J.Immunol.151. 4407-4413 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Takada et al.: "Cytokine induction by extracellular products of oral viridans group streptocci." Infect.Immun.61. 5252-5260 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Uchiyama et al.: "Mini Review.Bacterial superantigens-Mechanisms of T cell activation and their role in the pathogenesis fo infectious diseases." Microbiol.Immunol.(in press.). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] J.Yan et al.: "Superantigenic properties of an antibode bispecific for MHC class II molecules and the Vbeta domain of the T cell antigen receptor." J.Immunol.(in press.). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Akatuka et al.: "Production of tumor necrosis factors by human T cellsstimulated by a superantigen,toxic shock syndrome toxin-1.(in press.)" Clin.exp.Immunol.(1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] J.Yagi et al.: "Stimulatory cell type influences the repertoire of T cells responding to staphylococcal enterotoxins.(in press.)" J.Immunol.(1994)

    • Related Report
      1993 Annual Research Report

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

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