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Studies on differentiation, maturation and activation of human T cells

Research Project

Project/Area Number 10670272
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionTokyo Women's Medical University School of Medicine

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) FUJIMAKI Wakae  Tokyo Women's Medical University, Instructor, 医学部, 助手 (90256496)
YAGI Junji  Tokyo Women's Medical University, Assistant Professor, 医学部, 講師 (70182300)
UCHIYAMA Takehiko  Tokyo Women's Medical University, Professor, 医学部, 教授 (00050550)
MIYOSHI-AKIYAMA Tohru  Tokyo Women's Medical University, Instructor, 医学部, 助手 (20246466)
KATO Hidehito  Tokyo Women's Medical University, Instructor, 医学部, 助手 (00241084)
田中 義正  東京女子医科大学, 医学部, 助手 (90280700)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsT cells / differentiation / maturation / activation / superantigen / 胸腺 / 臍帯血 / アナジー
Research Abstract

1. We examined the responses of different stages of CD4 single positive (SP) T cells to a superantigen, TSST-1. The following results were obtained. (1) Thymic CD1a^-CD4 SP T cells are functionally mature, but CD1a^+CD4 SP T cells are not. (2) Thymic CD1a^- and cord blood (CB) CD4^+ T cells are susceptible to anergy induction, while adult peripheral blood (APB) CD4^+ T cells are not. The susceptibility to it is higher in thymic T cells than in CB T cells. (3) The majority of thymic and CB T cells are CD38^+, while CD38 expression in APB T cells is varied. Both APB CD38^+ and CD38^- CD4^+ T cells are not susceptible to anergy induction. (4) APB CD38^+CD4^+ T cells are weak in a potential to produce IL-4 and IFN-γ, while CD38^- T cells have the high potential. These results suggest that post-thymic maturation is required for thymic T cells migrating to the periphery to acquire full immunologic capability to the antigenic stimulation.
2. Studies on signal transduction in thymic and APB CD4 … More ^+ T cells suggest that absence of an interaction between Lck and CD45 is responsible for maintaining the anergic state of thymic CD1a^- CD4^+ T cells induced by TSST-1.
3. We discovered an emerging neonatal infectious disease, neonatal toxic shock syndrome-like exanthematous disease (NTED), which is induced by TSST-1 produced by methicilllin-resistant Staphylococcus aureus (MRSA). Then, we analyzed the activation and the response of TSST-1-reactive Vβ2^+ T cells in NTED patients during the acute and recovery phases and in asymptomatic infants exposed to MRSA.In the acute phase, Vβ2^+ T cells were anergic to stimulation with TSST-1 and underwent marked expansion, but by 2 months after disease onset, their number had declined to about 10% of the control level. On the basis of Vβ2^+ T cells activation, asymptomatic neonatal MRSA carriers were divided to two types ; type 1, Vβ2^+ T cells were activated by TSST-1 ; type 2, Vβ2^+ T cells were intact. We also observed protective role of anti-TSST-1 IgG of maternal origin against the influence of TSST-1. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 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"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
      2000 Final Research Report Summary
  • [Publications] 八木淳二: "Identification of a new type of invariant Vα 14+ T cells and responsiveness to a superantigen, Yersinia pseudotuberculosis-deraived mitogen."J.Immunol.. 163. 3083-3091 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 今西健一: "Post-thymic maturation of migrating human thymic single positive T cells : Thymic CD1a-CD4+ T cells are more susceptible to anergy induction by toxic shock syndrome toxin-1 than cord…"J.Immunol.. 160. 112-119 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 高橋尚人: "Exanthematous disease induced by toxic shock syndrome toxin-1 in the early neonatal period."Lancet. 351. 1614-1619 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 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."J.Biol.Chem.. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Takahashi: "Immunopathophysiological aspects of en 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
      2000 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
      2000 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
      2000 Final Research Report Summary
  • [Publications] K.Imanishi: "Post-thymic maturation of migrating human thymic single positive T cells : Thymic CD1a^-CD4^+ T cells are more susceptible to anergy induction by toxic shock"J.Immunol.. 160. 112-119 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Takahashi: "Exanthematous disease induced by toxic shock syndrome toxin-1 in the warly neonatal period."Lancet. 351. 1614-1619 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 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.. in press. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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-"Biothecrapy. 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
  • [Publications] 今西 健一: "Post-thymic maturation of Migrating human thymic single-positive T cells." J.Immunol.160. 112-119 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高橋 尚人: "Exanthematous disense induced by toxic shock syndrome toxin-1 in the early neonatatal period." Lancet. 351・9116. 1614-1619 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2021-11-25  

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