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Multiple analysis of the pathogenic mechanism of an re-emerging infectious disease, neonatal TSS-like exanthematous disease and related diseases

Research Project

Project/Area Number 11470072
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionTokyo Woman's Medical University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) YAGI Junji  Tokyo Women's Medical University, School of Medicine, Lecture Instructor, 医学部, 講師 (70182300)
IMANISHI Kenichi  Tokyo Women's Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (20132920)
今西 健一  東京女子医科大学, 医学部, 助教授 (80124527)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1999: ¥5,300,000 (Direct Cost: ¥5,300,000)
KeywordsTSS / TSST-1 / superantigen / Tcell / NTED / SDM / TSST-1 / スーパー抗原 / MRSA / Vβ2^+T細胞 / トキシックショック症候群 / 新生児TSS様発疹 / T細胞 / TCRVβ
Research Abstract

In 1998 we have clarified the pathogenic mechanism of an infectious disease caused by a superantigenic toxin, and designated this disease neonatal TSS-like exanthematous disease (NTED). Under the current project, we examined following subjects.
1) T cell response in patients with NTED: TSST- 1-reactive T cells increased to 3-fold the control level in the acute phase and decreased to 20% of the control level 1-2 months later. TSST-1-reactive CD4+ T cells in expanded state are in an anergic state. The presence of IgG-type antibodies to TSST-1 prevented manifestation of clinical symptoms in MRSA neonatal carriers.
2) Responsibility of T cell in neonates: We obtained data suggesting that susceptibility of T cells in neonates to anergy induction to TSST-1 is caused by an inability of tyrosine-kinase Lck to make functional association with tyrosine-phosphatase CD45. 3) Superantigen-induced T cell response in mice: Using mice implanted with an osmotic pump filled with SEA, it was found that SEA-reactive CD4+ T cells exhibited protracted expansion and a memory-type response. 4) Discovery of a new type of superantigenic toxin: We found a new type of superantigenic toxin, Streptococcus dysgalactiae-derived mitogen which activates Yβ1 + and Vβ23+ T cells in association with MHC class II molecules on antigenpresenting cells.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] N.Takahashi., et al.: "Immunopathophysiological aspects of an emerging neonatal infectious disease induced by a bacterial superantigen"J. Clin. Invest.. 106. 1409-1415 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] W.Fujimaki., et al.: "Functional uncoupling of T-cell receptor engagement and Lck activation in anergic human thymic CD4+ T cells"J. Biol. Chem.. 276. 17455-17460 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Shiseki et al.: "Comparison of pathogenic factors expressed by group A Streptococci isolated from patients with streptococcal toxic shock syndrome and scarlet fever."Microbial Pathogenesis. 27. 243-252 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] J. Yagi et al.: "Identification of a new type of invariant Vβ14+ T cells and responsiveness to a superantigen, Yersinia pseudotuberculosis-derived mitogen."J. Immunol.. 163. 3083-3091 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Uchiyama et al.: "The pathogenesis of Kawasaki disease and superantigens."Jpn. J. Infect. Dis.. 52. 141-145 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] R. Zhang et al.: "Different behaviors of distinct murine T cell populations reactive with a bacterial superantigen, staphylococcal enterotoxin A upon in vivo stimulation."J. Tokyo Wom. Univ. 69. 659-668 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Saito et al.: "Rhabdomyolysis and aggravation of a arthritis in a rheumatoid arthritis patient as a result of sepsis due to Staphylococcus aureus infection of a rheumatoid nodule; a catastrophic outcome."Fukushima J. Med. Sci.. 45. 125-133 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Sawaguchi et al.: "Factors related to the autonomic nervous system in sudden death of adults and infants with special reference to the circulatory system."Acta Crim. Japon. 66. 56-68 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] L. Chen et al.: "Susceptibility to in vitro induction of four murine T-cell fractions reactive with staphylococcal enterotoxin A superantigen."J. Tokyo Wom. Med. Univ. 70. 693-701 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Takahashi et al.: "Immunopathophysiological aspects of an emerging neonatal infectious disease induced by a bacterial superantigen."J. Clin. Invest.. 106. 1409-1415 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Takeda et al.: "Recurrent septicemia caused by strreptococcus canis after a dog bite."Scand. J. Infect. Dis.. 33. 927-928 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimaki et al.: "Functional uncoupling of T-cell receptor engagement and Lck activation in anergic human thymic CD4+ T cells."J. Biol. Chem.. 276. 17455-17460 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Kobayashi et al.: "Gamma/delta T cells provide innate immunity against renal cell carcinoma."Cancer Immunol. Immunother.. 50. 115-124 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Kato et al.: "Superantigen-reactive Vb2+ T cells exhibit a significant reduction before their massive increase in some acute phase patients with TSS-like exanthematous disease."J. Infect Chemother. (in print).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Arimura et al.: "A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in Th cells and regulates their responses."Int. Immunol.. (in print).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] L. Chen et al.: "Continuous exposure of mine to superantigenic toxins induces a high-level protracted expension and an immunological memory in the toxin-reactive CD4+ T cells."J. Immunol.. (in print).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N.Takeda et al.: "Recurrent septicemia caused by Streptococcus canis after a dog bite"Scand. J. Infect. Dis. 33. 927-928 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] W.Fujimaki et al.: "Functional uncoupling of T-cell receptor engagement and Lck activation in anergic human thymic CD4+ T cells"J. Biol. Chem.. 276. 17455-17460 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Kobayashi et al.: "Gamma/delta T cells provide innate immunity against renal cell carcinoma"Cancer Immunol. Immunother.. 50. 115-124 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 張 華 他: "ヒト末梢血のCD4+T細胞とCD8+T細胞における細菌性スーパー抗原に対する反応性の相違"東京女子医大誌. 71. 387-397 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Arimura et al.: "A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in Th cells and regulated their responses"Int. Immunol.. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] L. Chen et al.: "Continuous exposure of mice to superantigenic toxins induces a high-level protracted expansion and an immunological memory in the toxin・・・・"J. Immunol.. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Takahashi, et al.: "Immunopathological aspects of an emerging neonatal infectious disease induced by a bacterial superantigen "J Clin Invest. 106. 1409-1415 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Kobayashi, et al.: "gamma-delta T cell provide innate immunity against renal cell carcinoma"Cancer Immunol Immunotherapy. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Saito, et al: "Rhabdomyolysis and aggravation of arthritis in a rheumatoid arthritis patients as a reseet of cepsis due to staphy lococcus aarens…"Fukushima J Med.Sci. 45. 125-133 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Sawaguchi et al: "Factors related to the autonomic nervous system in sidden death of adult and infauts."Acta Crim Japan. 66. 56-68 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] L.Chen, et al.: "Susceptibility to invitro anergy induction of four murine T cell fractions reactive with staphylococcus enterotoxin A superantigen"J.Tokyo Wom Mol Uwn. 70. 693-701 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] W.Fujimaki, et al.: "Functional uncoupling of TCR engagement and LcK activation in anergic human thymic CD4^+ T cells"J Biol Chem. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 内山竹彦 ほか: "生物間の功撃と防御の蛋白質"共立出版社. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Junji Yagi: "Identification of a new type of invariant V∂14^+ T cells and responsiveness to a superantigen, Yersinia pseudotuberculosis-derived mitogen"J. Immunol.. 163. 3083-3091 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masayuki Shiseki: "Comparison of pathogenic factors expressed by group A Streptococci isolated from patients with streptococcal toxic shock syndrome and scarlet"Microbial Pathogenesis. 27. 243-252 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takehiko Uchiyama: "The Pathogenesis of Kawasaki Disease and Superantigens"Jpn. J. Infect. Dis.. 52. 141-145 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 河内 章: "新しい微生物抗原,スーパー抗原-医学研究の新しい戦略-"Biotherapy. 13・3. 231-239 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 太刀川貴子: "各種病原微生物に対する弱酸性電解水の効果"環境感染. 14・4. 255-263 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 内山竹彦: "スーパー抗原という概念 疾患発症機序解析の戦略"アレルギー・免疫. 6・10. 89-96 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 畑中正一編: "微生物学"文光堂. 637 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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