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Study on human T cell changes in response to infections and applications

Research Project

Project/Area Number 11557023
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Bacteriology (including Mycology)
Research InstitutionTokyo Women's Medical University School of Medicine

Principal Investigator

IMANISHI Ken-ichi  Tokyo Women's Medical University School of Medicine, Microbiology and Immunology, Associate Professor, 医学部, 助教授 (20132920)

Co-Investigator(Kenkyū-buntansha) FUJIMAKI Wakae  Tokyo Women's Medical University School of Medicine, a medical school, Professor, 医学部, 助手 (90256496)
YAGI Junji  Tokyo Women's Medical University School of Medicine, a medical school, Professor, 医学部, 講師 (70182300)
UCHIYAMA Takehiko  Tokyo Women's Medical University School of Medicine, a medical school, Professor, 医学部, 教授 (00050550)
AKIYAMA TOHRU (MIYOSHI Tohru)  Tokyo Women's Medical University School of Medicine, a medical school, Professor, 医学部, 助手 (20246466)
KATO Hidehito  Tokyo Women's Medical University School of Medicine, a medical school, Professor, 医学部, 助手 (00241084)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1999: ¥8,800,000 (Direct Cost: ¥8,800,000)
KeywordsT cells / superantigen / infectious diseases / γδT cells / toxic shock syndrome / renal cell carcinoma / neonatal toxic shock syndrome-like exanthematous disease / TCR Vβ / Th1 / Th2
Research Abstract

1. By analyzing T cell receptor (TCR) Vβ2 vs CD45RO expression in T cells from patients with neonatal exanthematous disease in acute phase, we discovered an emerging neonatal infectious disease, neonatal toxic shock syndrome-like exanthematous disease (NTED), which is induced by TSST-1 produced by methicillin-resistant Staphylococcus aureus (MRSA). Using the same method, we provided early and definitive diagnosis of toxic shock syndrome (TSS). Furthermore, we observed that, in the early acute phase of NTED patients, there was a significant decrease in the percentage of Vβ2^+ T cells in peripheral blood T cells before the usual increase.
2. To see abnormal reactions seen in TSS we made two models using rabbits and mice by long-term exposure to superantigen in implanted osmotic pumps. In the model using rabbits, we observed acute and systemic abnormal reactions and very high mortality rate. In the model using mice, we found that the level of the superantigen-reactive CD4^+ T cell fraction … More s varies widely depending on TCR Vβ elements expressed and that the reactive CD4^+ T cells acquire a capacity to raise a memory response. CD8^+ T cells are low responders to superantigen.
3. The study of T cell changes in response to infection is useful not only for humans but also other animals. Streptococcus dysgalactiae-derived mitogen (SDM) was recently identified from a bovine isolate of S. dysgalactiae. A comparison of its effects on human and bovine PBMC revealed that it acts as a superantigen on both species. The superantigen SpeC, which is a product of the predominantly human pathogen Streptococcus pyogenes, also activates corresponding T cells in human and bovine systems. SDM however, has a much more potent effect on bovine cells than human cells and is more likely to have a pathogenic role in S. dysgalactiae infections of cows than humans.
4. It is known that human γδT cells defend the body against infection. We observed that the number of γδT cells was elevated in the peripheral blood in patients with renal cell carcinomas (RCC), and that the level of the γδT cells decreased after surgery. Our finding suggest that γδT cells provide innate immunity against RCC. Less

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (47 results)

All Other

All Publications (47 results)

  • [Publications] Mwaka Monze: "Superantigenic stimulation of bovine T cells by Streptococcus dysgalactiae-derived mitogen (SDM)"東京女子医科大学雑誌. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 松田義雄: "Early and definitive diagnosis of toxic shock syndrome by detection of marked expansion of T cell receptor Vβ2-positive T cells"Emerging Infectious Diseases. 9. 387-389 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 三好・秋山徹: "A novel vacterial superantigen, Strptococcus dysgalactiae-derived mitogen (sdm) -characterization of its blological activity and predicted tertiary structure"Molecular Microbiology. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 陳露秋: "Continuous exposure of mice to superantigenic toxins induces a high-level protracted expansion and an immunological memory in the toxin-reactive CD4^+ T cells"Journal of Immunology. 168. 3817-3824 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 加藤秀人: "The percentage of superantigen-reactive T cells in peripheral blood signiflcantly decreases before massively increasing in patients with neonatal TSS-like exanthematous disease in the early acute phase"Journal of Infection and Chemotherapy. 8. 111-114 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 内山竹彦: "新生児のMRSA感染症;新生児TSS様発疹症(NTED)とスーパー抗原性毒素"感染・炎症・免疫. 31. 198-206 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 小林博人: "Gamma/delta T cells provide innate immunity against renal cell carcinoma"Cancer immunology and Immunotherapy. 50. 115-124 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 藤巻わかえ: "Functional uncoupling of TCR engagement and Lck activation in anergic human thymic CD4^+ T cells"Journal of Biological Chemstry. 276. 17455-17460 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 高橋尚人: "Immunopathophysiological aspects of an emerging neonatal infectious disease induced by a bacterial superantigen"Journal of Clinical Investigation. 106. 1409-1415 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 今西健一: "ヒトT細胞の胸腺内および胸腺後の発達(CD4^+シングルポジティブT細胞について)"アレルギー・免疫. 6. 108-117 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 内山竹彦: "The pathogenesis of Kawasaki disease and superantigens"Japan Journal of infectious Diseases. 52. 141-145 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 河内章: "ブドウ球菌スーパー抗原TSST-1の長時間暴露によるウサギ毒素性ショック症候群の誘導とその病態の解析"東京女子医科大学雑誌. 69. 571-578 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Monze: "Superantigenic stimulation of bovine T cells by Streptococcus dysgalactiae-derived mitogen (SDM)."J. Tokyo Wom. Med. Univ.. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Matsuda: "Early and definitive diagnosis of toxic shock syndrome by detection of marked expansion of T cell receptor Vβ2-positive T cells."Emerg. Infect. Dis.. 9. 387-389 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Miyoshi-Akiyama: "A novel bacterial superantigen, Streptococcus dysgalactiae-derived mitogen (sdm) - characterization of its biological activity and predicted tertiary structure."Mol. Microbiol.. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] L. Chen: "Continuous exposure of mice to superantigenic toxins induces a high-level protracted expansion and an immunological memory in the toxin-reactive CD4^+ T cells."J. Immunol.. 168. 3817-3824 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Kato: "The percentage of superantigen-reactive T cells in peripheral blood significantly decreases before massively increasing in patients with neonatal TSS-like exanthematous disease in the early acute phase."J. Infect. Chemother.. 8. 111-114 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Arimura: "A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in Th cells and regulates their responses."Int. Immunol.. 14. 555-566 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Kobayashi: "Gamma/delta T cells provide innate immunity against renal cell carcinoma."Cancer Immunol. Immunother.. 50. 115-1124 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] W. Fujimaki: "Functional uncoupling of TCR 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
      2002 Final Research Report Summary
  • [Publications] N. Takahashi: "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
      2002 Final Research Report Summary
  • [Publications] K. Imanishi: "Intra- and post-thymic development of human T cells."Allergology & Immunology. 6. 108-117 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] J. Yagi: "Identification of a new type of invariant Vα14^+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
      2002 Final Research Report Summary
  • [Publications] T. Uchiyama: "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
      2002 Final Research Report Summary
  • [Publications] A. Kawachi: "Pathogenic mechanism of toxic shock syndrome in rabbits induced by long-term exposure to staphylococcal superantigen TSST-1."J. Tokyo Wom. Med. Univ.. 69. 571-578 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Monze: "Superantigenic stimulation of bovine T cells by Streptococcus dysgalactiae-derived mitogen (SDM)"東京女子医科大学雑誌. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松田義雄: "Early and definitive diagnosis of toxic shock syndrome by detection of marked expansion of T cell receptor V β 2-positive T cells"Emerg. Infect. Dis.. 9. 387-389 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 三好・秋山徹: "A novel bacterial superantigen, Streptococcus dysgalactiae-derived mitogen (sdm) -charcterization of its biological activity and predicted tertiary"Mol Moicrobiol. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 陳露秋: "Continuous exposure of mice to superantigenic toxins induced a high-level protracted expansion and immunological memory in the toxin-reactive"J. Immunol. 168. 3817-3824 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 加藤秀人: "The percentage of superantigen-reactive T cells in peripheral blood significantly decreases before massively increasing in patients with neonatal"J. Infect. Chemother. 8. 111-114 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 有村裕: "A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in Th cells andregulates their responses"Int. Immunol. 14. 555-566 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤巻わかえ: "Functional uncoupling of TCR engagement and Lck activation in anergic human thymic CD4^+ T cells"J. Biol. Chem.. 276・20. 17455-17460 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 張華: "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"J. Tokyo Woman's Med. Univ.. 77・7. 387-397 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 内山竹彦: "新生児のMRSA感染症;新生児TSS様発疹症(NTED)とスーパー抗原性毒素"感染・炎症・免疫. 31・3. 198-206 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 小林博人: "Bamma/delta T cells provide innate immunity against renal cell carcinoma"Cancer Immunol. Immunother.. 50. 115-124 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 加藤秀人: "The percentage of superantigen-reactive T cells in peripheral blood significantly decreases before massively increasing in patients with neonatal"J. Infect. Chemother.. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 陳露秋: "Continous exposure of mice to superantigenic toxins induces a high-level protracted expansion and an immunological memory in the toxin-reactive"J. Immunol.. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高橋尚人: "Immunophathophysiological 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] 陳露秋: "Susceptibility to in vitro anergy induction of four murine T-cell fractions reactive with staphylococcal enterotoxin A superantigen."J.Tokyo Women's Med.Univ.. 70. 693-701 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 藤巻わかえ: "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] 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] 今西健一: "ヒトT細胞の胸腺内および胸腺後の発達(CD4^+シングルポジティブT細胞について)"アレルギー・免疫. 6・4. 616-625 (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: 2021-11-25  

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