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1999 Fiscal Year Final Research Report Summary

Allergic inflammation model of the human airways by using SCID-hu Chimera: application for asthma therapy

Research Project

Project/Area Number 10670553
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKumamoto University

Principal Investigator

KOHROGI Hirotsugu  Kumamoto University, University Hospital, Assistant Professor, 医学部・附属病院, 講師 (00178237)

Co-Investigator(Kenkyū-buntansha) ANDO Masayuki  Kumamoto University School of Medicine, Professor, 医学部, 教授 (00040204)
Project Period (FY) 1998 – 1999
Keywordsasthma / inflammation / i-IELs / bronchus / allergy / lymphocytes / SCID mouse
Research Abstract

Intestinal intraepithelial T lymphocytes (i-IELs) show features different from those of conventional T cells and play specific roles in the mucosal immunity. To investigate whether human bronchial intraepithelial T lymphocytes (IELs) are a distinct entity, we examined T cells in human bronchial xenografts transplanted on mice with severe combined immune deficiency (SCID). We transplanted human bronchi subcutaneously into mice with SCID, resected the xenografts after various incubation periods (7-174 d), and examined them for CD3+, CD4+, CD8+, and CD45+ cells by immunohistochemistry. The number of CD3+ cells in the lamina propria decreased significantlly in the first month, and xenografts more than 5 mo of age had scant T cells in the lamina propia. However, there was no significant difference between the number of CD3+ IELs in freshly isolated bronchi and in xenografts maintained for more than 5 mo. In freshly isolated bronchi, the number of CD4+ IELs was significantly lower than that of CD8+ cells. After transplantation, the mean CD4-to-CD8 ratio of all xenografts was significantly higher than that of freshly isolated bronchi. The IELs were positive for CD45, which is specific for human leukoctes, and they were eliminated by irradiation before the transplantation. Almost all IELs (99.5%) in the xenografts expressed αβT-cells receptor, and 35.8% of IELs expressed αeβ7 integrin. Bronchial epithelial cells in the xenografts expressed interleukin (IL)-7, stem cell factor , intercellular adhesion molecule (ICAM)-1, and human leukocyte antigen-DR (HLA-DR). We conclude thaat in the SCID-Hu chimera model, human bronchial IELs survive for more than 5 mo, unlike the T cells in the lamina propria, and we suggest that human bronchial IELs may be stimulated by broncial epithelial cells expressing IL-7, stem cell factor, ICAM-1, and HLA-DR.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Eisuke Goto: "Human bronchial intra-epithelial T lymphocytes as a distinct T cell subset: Their long-term survival in SCID -hu chimeras"Am. J. Respir. Cell. Mol. Biol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirotsugu Kohrogi: "Clinical conference: insidious onset asthma without episodic dyspnea"Internatiol Review of Asthma. 1. 88-93 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirotsugu Kohrogi: "The role of cysteinyl leukotrienes in the pathogenesis of asthma: clinical study of leukotriene pranlukast for one year in moderate and severe asthma"Respirology. 4. 319-323 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平田 奈緒美: "喘息予防・管理ガイドライン"医薬ジャーナル. 35・11. 2883-2886 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 興梠 博次: "慢性咳嗽の治療と神経ペプチド"治療. 81(増刊号). 72-75 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] "気管支喘息における咳嗽の機序とその制御"アレルギー科. 6. 431-436 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 後藤 英介: "アレルゲン特異的T細胞におけるホーミングレセプター発現 気道過敏性研究1999"相澤久道、浅井貞宏、久保千春、興梠博次. 40 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 濱本 淳二: "気管支喘息患者気道組織における樹状細胞の免疫組織化学的検討 気道過敏性1998"相澤久道、浅井貞宏、久保千春、興梠博次. 41 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] E. Goto, H. Kohrogi, N. Hirata, K.Tsumori, S. Hirasako, J. Hamamoto, K. Fujii, O. Kawano, M.Ando: "Human brochial intra-epithelial T lymphocytes as a distinct T cell subset: Their long-term survival in SCID-hu chimeras"AM. J. Respir. Cell Mol. Biol.. 22. 405-411 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Kohrogo,M. Ando: "Clinical confernce: insidious onset asthma without episodic dyspnea"International Review of Asthma. 1. 88-93 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Kohrogi, H. Iwagoe, K. Fujii, J. Hamamoto, K. Fukuda, N. Hirata, O. Kawano, M.Matsumoto, M Suga, M. Ando: "The role of cysteinyl leukotrienes in the pathogenesis of asthma: clinical study of leukotriene antagonist pranlukast fo one year in moderate and severe asthma"Respirology. 4. 319-323 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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