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Basic studies for induction of tolerance by a cell-therapy

Research Project

Project/Area Number 25670548
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionHokkaido University

Principal Investigator

YAMASHITA KENICHIRO  北海道大学, 医学(系)研究科(研究院), 特任教授 (00399940)

Co-Investigator(Kenkyū-buntansha) GOTO Ryoichi  北海道大学, 北海道大学病院, 医員 (10645287)
AOYAGI Takeshi  北海道大学, 北海道大学病院, 医員 (90374347)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords移植免疫 / 免疫抑制性 / 細胞治療 / 分子標的 / 免疫抑制性細胞
Outline of Final Research Achievements

In this study, we performed basic researches on immunoregulatory cells in order to search for new immunosuppressive strategies. We found that tolerogeneic dendritic cells (tDCs) were successfully generated ex-vivo by suppressing activation of either NF-κB or MAPKs in the presence of donor-peptide antigens, and that administration of these tDCs significantly prolonged allograft survival in mice. The inhibition of NF-κB, MAPKs or AP-1/mTOR/p70S6K activation following infusion of donor-leukocytes exerted a potent immunosuppressive effect. In some of these protocols, regulatory T cells (Tregs) were effectively induced in vivo. Coculture of peripheral blood mononuclear cells and allo-antigens together with either CD80/86- or CD40-costimulation blockers induced antigen-specific Tregs that seemed to have a potential utility for clinical immunosuppression.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (7 results)

All 2014 2013

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (6 results)

  • [Journal Article] Immunosuppressive effects of DTCM-G, a novel inhibitor of the mTOR downstream signaling pathway.2013

    • Author(s)
      Shibasaki S
    • Journal Title

      Transplantation

      Volume: 95 Issue: 4 Pages: 542-550

    • DOI

      10.1097/tp.0b013e31827b3d90

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] NK026680とdonor specific transfusion併用による免疫修飾効果2014

    • Author(s)
      江本 慎、後藤了一、柴崎 晋、長津明久、小野 仁、青柳武史、深井 原、武冨紹信、嶋村 剛、藤堂 省、山下健一郎
    • Organizer
      第50回日本移植学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2014-09-10 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Immunomodulation induced by a novel immunosuppressant, NK026680 plus donor specific transfusion permits a long-term cardiac allograft survival in mice2014

    • Author(s)
      Emoto S, Goto R, Shibasaki S, Nagatsu A, Ono H, Igarashi R, Aoyagi T, Fukai M, Shimamura T, Saiga K, Taketomi A, Todo S, Yamashita K
    • Organizer
      World Transplant Congress 2014
    • Place of Presentation
      Moscone West Convention Center, San Francisco, CA, USA
    • Year and Date
      2014-07-26 – 2014-07-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Inducion of Operational Tolerance by a Cell Therapy using Donor Ag-pulsed Tregs in Living Donor Liver Transplantation2014

    • Author(s)
      Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, Watanabe M, Aoyagi T, Suzuki T, Shimamura T, Kamiyama T, Sato N, Sugita J, Hatanaka K, Demetris AJ, Bashuda H, Okumura K, Todo S
    • Organizer
      World Transplant Congress 2014
    • Place of Presentation
      Moscone West Convention Center, San Francisco, CA, USA
    • Year and Date
      2014-07-26 – 2014-07-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Successful Withdrawal of Immunosuppression by a Cell Therapy Using Donor Ag-pulsed Tregs in Living Donor Liver Transplantation2014

    • Author(s)
      Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, Watanabe M, Aoyagi T, Suzuki T, Shimamura T, Kamiyama T, Sato N, Sugita J, Hatanaka K, Bashuda H, Okumura K, Todo S
    • Organizer
      2014 Joint International Congress of ILTS, ELITA & LICAGE
    • Place of Presentation
      Queen Elizabeth II Conference Center, London, UK
    • Year and Date
      2014-06-04 – 2014-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗CD80抗体、抗CD86抗体下共培養により誘導される免疫抑制性細胞の同定2014

    • Author(s)
      長津明久、山下健一郎、江本 慎、旭 火華、財津雅昭、小倉正臣、小野 仁、常俊雄介、後藤了一、五十嵐瑠美、場集田 寿、奥村 康、武冨紹信、藤堂省
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      京都国際会館(京都市)
    • Year and Date
      2014-04-03 – 2014-04-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] EX-VIVO GENERATION OF HUMAN REGULATORY T CELLS BY CD80/CD86 COSTIMULATION BLOCKADE2013

    • Author(s)
      Akihisa Nagatsu, Kenichiro Yamashita, Masaaki Zaitsu, Shin Emoto, Yoh Asahi, Hitoshi Ono, Ryoichi Goto, Hisashi Bashuda, Akinobu Taketomi, Ko Okumura, Satoru Todo
    • Organizer
      16th Congress of the European Society for Organ Transplantation
    • Place of Presentation
      Austria Centre Vienna (ACV), Vienna, Austria
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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