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Involvement of DNAM-1 in the development of graft-versus-host disease

Research Project

Project/Area Number 21890026
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionUniversity of Tsukuba

Principal Investigator

NABEKURA Tsukasa  University of Tsukuba, 大学院・人間総合科学研究科, 研究員 (80550095)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2010: ¥1,235,000 (Direct Cost: ¥950,000、Indirect Cost: ¥285,000)
Fiscal Year 2009: ¥1,365,000 (Direct Cost: ¥1,050,000、Indirect Cost: ¥315,000)
Keywords移植片対宿主病 / GVHD / DNAM-1 / 抗体療法 / 骨髄移植
Research Abstract

Graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation ; however, no effective molecular targeting therapy has been determined. Here, we show that mice that received allogeneic splenocytes deficient in DNAM-1 had significantly lower mortality than those that received wild-type (WT) splenocytes. Donor CD8+T cells deficient in DNAM-1 showed less proliferation and produced less interferon-γ after coculture with allogeneic splenocytes than WT CD8+ T cells. Mice prophylactically treated with an anti-DNAM-1 antibody showed low mortality. Moreover, treatment with a single administration of the antibody after the onset of GVHD prolonged survival. These results indicate that DNAM-1 plays an important role in the development of GVHD and is an ideal molecular target for therapeutic approaches to GVHD.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (17 results)

All 2011 2010 2009 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (11 results) Remarks (2 results)

  • [Journal Article] DNAX accessory molecule-1 (DNAM-1) plays an important role in alloreactive CD8+ T cells responsible for the exacerbation of acute graft-versus-host disease2011

    • Author(s)
      Tsukasa Nabekura, Kazuko Shibuya, Akira Shibuya、Reply to Seth, et al.
    • Journal Title

      Proc Natl Acad Sci USA 108

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reply to Seth et al. : DNAX accessory molecule-1 (DNAM-1) plays an important role in alloreactive CD8+ T cells responsible for the exacerbation of acute graft-versus-host disease2011

    • Author(s)
      Tsukasa Nabekura, Kazuko Shibuya, Akira Shibuya
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: Vol.108

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A critical role of DNAM-1 in the development of acute graft-versus-host disease in mice2010

    • Author(s)
      Tsukasa Nabekura, Kazuko Shibuya, Eri Takenaka, Hirayasu Kai, Kai Shibata, Yumi Yamashita, Kyoichi Harada, Satoko Tahara-Hanaoka, Shin-ichiro Honda, Akira Shibuya
    • Journal Title

      Proc Natl Acad Sci USA 107

      Pages: 18593-18598

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A critical role of DNAM-1 in the development of acute graft-versus-host disease in mice2010

    • Author(s)
      Tsukasa Nabekura, Kazuko Shibuya、, Eri Takenaka, Hirayasu Kai, Kai Shibata, Yumi Yamashita, Kyoichi Harada, Satoko Tahara-Hanaoka, Shin-ichiro Honda, Akira Shibuya
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: Vol.107 Pages: 18593-18598

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] A critical role of DNAM-1 in the development of acute graft-versus-host disease2011

    • Author(s)
      鍋倉宰
    • Organizer
      第5回つくば医科学研究交流会
    • Place of Presentation
      筑波大学(茨城県)
    • Year and Date
      2011-01-22
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 抗DNAM-1モノクローナル抗体を用いた移植片対宿主病に対する新規予防および治療法の開発2010

    • Author(s)
      鍋倉宰
    • Organizer
      第2回造血器腫瘍免疫療法研究会
    • Place of Presentation
      大和屋本店(愛媛県)
    • Year and Date
      2010-08-28
    • Related Report
      2010 Final Research Report
  • [Presentation] A critical role of DNAM-1 in the development of acute graft-versus-host disease2010

    • Author(s)
      鍋倉宰
    • Organizer
      第2回造血器腫瘍免疫療法研究会
    • Place of Presentation
      大和屋本店(愛媛県)
    • Year and Date
      2010-08-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] A critical role of DNAM-1 in the development of acute graft-versus-host disease2010

    • Author(s)
      鍋倉宰
    • Organizer
      The 14th International Congress of Immunology
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Year and Date
      2010-08-26
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] DNAM-1は移植片対宿主病の発症において重要な役割を果たす2010

    • Author(s)
      鍋倉宰
    • Organizer
      第20回京都T細胞カンファレンス
    • Place of Presentation
      京都大学(京都府)
    • Year and Date
      2010-06-05
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] A critical role of DNAM-1 in the development of acute graft-versus-host disease2010

    • Author(s)
      鍋倉宰
    • Organizer
      The Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Beaver Run Resort(コロラド州、米国)
    • Year and Date
      2010-03-01
    • Related Report
      2010 Final Research Report
  • [Presentation] A critical role of DNAM-1 in the development of acute graft-versus-host disease2010

    • Author(s)
      鍋倉宰
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology(Lymphocyte Activation)
    • Place of Presentation
      Beaver Run Resort、Breckenridge、コロラド州、米国
    • Year and Date
      2010-03-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] 抗DNAM-1モノクローナル抗体を用いた移植片対宿主病に対する新規予防および治療法の開発2009

    • Author(s)
      鍋倉宰
    • Organizer
      第39回日本免疫学会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2009-12-03
    • Related Report
      2010 Final Research Report
  • [Presentation] Novel prophylactic and therapeutic approaches to GVHD with a monoclonal antibody against DNAM-12009

    • Author(s)
      鍋倉宰
    • Organizer
      第39回日本免疫学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2009-12-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 抗DNAM-1モノクローナル抗体を用いた移植片対宿主病に対する新規予防および治療法の開発2009

    • Author(s)
      鍋倉宰
    • Organizer
      第71回日本血液学会
    • Place of Presentation
      京都国際会館(京都府)
    • Year and Date
      2009-10-23
    • Related Report
      2010 Final Research Report
  • [Presentation] Novel prophylactic and therapeutic approaches to GVHD with a monoclonal antibody against DNAM-12009

    • Author(s)
      鍋倉宰
    • Organizer
      第71回日本血液学会
    • Place of Presentation
      京都国際会館
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ等筑波大学免疫学研究室

    • URL

      http://www.immunologylab-tsukuba.org/

    • Related Report
      2010 Final Research Report
  • [Remarks] 筑波大学免疫学研究室

    • URL

      http://www.immunologylab-tsukuba.org/

    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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