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Clonal accumulation of T cells that recognize the dust mite antitgen of Dermatophagoides pteronyssinus in the skin lesion of atopic dermatitis

Research Project

Project/Area Number 10670810
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

MIZOGUCHI Masako  Professor & Director, Dept of Dermatol, St.Marianna Univ., 医学部, 教授 (30010250)

Co-Investigator(Kenkyū-buntansha) 西岡 久寿樹  聖マリアンナ医科大学, 難病治療研究センター, 教授 (60049070)
河 陽子  聖マリアンナ医科大学, 医学部, 助手 (10082273)
TAKAHAMA Hideto  Assistant, Dept of Dermatol, St.Marianna Univ., 医学部, 助手 (90267633)
KUSUKI Nishioka  Professor & Director, Institute of Medical Science, St.Marianna Univ.
YOKO Kawa  Assistant, Dept of Dermatol, St.Marianna Univ.
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsAtopic Dermatitis / T cell clone / T cell receptor / RT-PCR / SSCP / Dermatophagoides pteronycsinus(Dp)
Research Abstract

Involvement of T cell-mediated immune response, especially that toward the house dust mite (HDM) antigens, has been suggested in atopic dermatitis (AD). Although oligoclonal T cell accumulation in the skin lesion of AD has been observed, the exact target antigen in vivo has not been identified. We here investigated whether such skin-infiltrating T cells clones recognize HDM by analyzing T cell receptor (TCR) B genes. Specifically, peripheral blood mononuclear cells (PBMC) obtained from six AD patients, who showed high anti-HDM IgE titer, were cultured with HDM antigens purified from Dermatophagoides pteronyssinus (Dp). TCR B genes of the HDM-stimulated T cells in vitro were analyzed by the combination of reverse transcription polymerase chain reaction (RT-PCR) and subsequent single strand comformation polymorphism (SSCP) methods and then compared to that of T cells accumulated in the AD skin lesion in vivo. Nucleotide sequences of the TCR were also determined. Dp stimulation induce oligoclonal T cell expansion from the originally heterogeneous peripheral T cell population of AD patients. Moreover, several Dp-responding T cell clones were identical to the in vivo accumulating clones in the AD skin lesion, indicating the antigen-specific clonal accumulation of the skin-infiltrating T cells. These findings first demonstrated that the clonally accumulating T cells in the AD skin lesion, at least in part, are actually recognizing the Dp antigen in vivo as a specific target of their cellular immune response. Targeting of such T cells may lead to antigen-specific therapy for AD.

Report

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

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Takahama H et al. (Mizoguchi M): "Accumulation of T cell clonotypes in the skin lesions of patients with psoriasis vulgaris"J. Invest Dermatol. 114(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurakawa M et al (Nishioka K): "Characterization of T cell clonotypes that accumulated in multiple joints of patients with rheumatoid arthritis"Annals of the Rheumatic Diseases. 58・9. 546-553 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi K. et al (Nishioka K): "Clonal expansion of T cells that are specific for autologous ovarian tumor among tumor-infiltrating T cells in humans"Gynecologic Oncology. 74・1. 86-92 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka A. et al (Nishioka K, Mizoguchi M): "Clonotypic analysis of T cell infiltrating the skin of patients with atopic dermatitis : Evidence of antigen-driven accumulation of T cells"Human Immunol. 48. 107-113 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahama H, et al. (Mizoguchi M): "Accumulation of T cell clonotypes in the skin lesions of patients with psoriasis vulgaris(abstract)"I Invest Dermatol. 114(in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kurokawa M. et al. (Nishioka K): "Characterisation of T cell clonotypes that accumulated in multiple joints of patients with rheumatoid arthritis."Annals of the Rheumatic Disease. 58(9). 546-553 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi et al. (Nishioka K): "Clonal expansion of T cells that are specific for autologous ovarian tumor among tumor-infiltrating T cells in humans"Gynecologic Oncology. 74(1). 86-92 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka A, et al. (Nishioha K, Mizoguchi M): "Clonotypic analysis of T cells infiltrating the skin of patients with atopic dermatitis : Evidence for antigen-driven accumulation of T cells"Human Immuol. 48. 107-113 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahama H, et al(Mizoguchi H): "Accumulation of T. cell clonotypes in the skin lesions of patients with psoriasis vulgaris"J. Invest Dermatol. 114(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurakawa H, et al.(Nishioka K): "Characterisation of T cell clonotypes that accumulated in multiple joints of patients with rheumatoid arthritis"Annals of the Rheumatic Diseases. 58・9. 546-553 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi K, et al.(Nishioka K): "Clonal expansion of T cells that are specific for autologous ovarian tumor among tumor-infiltrating T cells in humans"Gynecologic Oncology. 74・1. 86-92 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka A, et al.(Nishioka K, Mizoguchi M): "Clonotypic analysis of T cell infiltrating the skin of patients with atopic dermatitis: Evidence of antigen-driven accumulation o T cells"Human Immunol. 48. 107-113 (1996)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka A et al(Mizoguchi): "Clonotypic analysis of T cells infiltrating the skin of patients with atopic dermatitis:Evidence for antigen-driven accumulation of T cells." Human Immunology. 48. 107-113 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] H Takahama et al: "IgE memory B cells identified by the polymerase chain reaction" Cellular Immunology. 176. 34-40 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kunisada T et al(Mizoguchi): "Murine cutaneous mastocytosis andepidermal mnelanocytosis induced by kdratinocyte expression oftransgenic stem cell factor" J Experimental Medicine. 187. 1565-1573 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小原理ら(溝口): "アトピー性皮膚炎におけるinterleukin-13(IL13)の関与" 日本免疫学会総会・学術集会記録. 28. 155 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masuko-Hongo K et al(Nishioka): "Frequent clonal expansion of peripheral T cells in patients with autoimmune diseases: a novel detecting system possibly applicable to laboratory examination." J Clinical Laboratory Analysis. 12. 162-167 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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