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Development of novel cellular therapy for T cell mediated rejection via direct and indirect pathway using regulatory liver sinusoidal endothelial cells (LSEC) in transplantation

Research Project

Project/Area Number 21890155
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionHiroshima University

Principal Investigator

ONOE Takashi  Hiroshima University, 病院, 病院助教 (90549809)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000)
Fiscal Year 2010: ¥1,235,000 (Direct Cost: ¥950,000、Indirect Cost: ¥285,000)
Fiscal Year 2009: ¥1,417,000 (Direct Cost: ¥1,090,000、Indirect Cost: ¥327,000)
Keywords肝移植 / 免疫寛容 / 移植免疫 / 類洞内皮細胞 / キメラ / PD-L1
Research Abstract

We have shown that liver sinusoidal endothelial cells (LSEC) has antigen specific immune-suppressive potential in vitro. In this study, we evaluated the possibility that adoptive transfer of isolated allogeneic LSECs induce immune-tolerance in vivo mouse model. Allogeneic BALB/cA LSECs were intraportally injected into immunodeficient RAG2/gc double-knockout (DKO) mice. After orthotopic allogeneic LSEC engraftment, engrafted LSECs expressed PD-L1 molecule. DKO mice were immune-reconstituted using C57BL/6 syngeneic splenocytes. After immune reconstitution, mixed lymphocyte reaction revealed specific inhibition of host alloreactive T-cell proliferation. Furthermore, allogeneic LSEC engraftment significantly prolonged subsequently grafted cognate allogeneic heart survival in DKO mice immune-reconstituted with syngeneic bone marrow transplantation. In conclusion, murine LSECs are capable of suppressing T cells with specificity cognate to LSECs in an in vivo model.

Report

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

    (23 results)

All 2010 2009 Other

All Journal Article (5 results) (of which Peer Reviewed: 3 results) Presentation (17 results) Remarks (1 results)

  • [Journal Article] T細胞の経口トレランス誘導と肝類洞内皮細胞2010

    • Author(s)
      尾上隆司
    • Journal Title

      臨床免疫・アレルギー科 54巻

      Pages: 601-604

    • NAID

      40017405375

    • Related Report
      2010 Final Research Report
  • [Journal Article] Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs.2010

    • Author(s)
      Onoe T, Kalscheuer H, et al.
    • Journal Title

      J Immunol 184(12)

      Pages: 6756-6765

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Distinct requirements for achievement of allotolerance versus reversal of autoimmunity via nonmyeloablative mixed chimerism induction in NOD mice.2010

    • Author(s)
      Nikolic B, Onoe T, et al.
    • Journal Title

      Transplantation 89(1)

      Pages: 23-32

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] T細胞の経口トレランス誘導と肝類洞内皮細胞2010

    • Author(s)
      尾上隆司
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 54 Pages: 601-604

    • NAID

      40017405375

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs.2010

    • Author(s)
      Onoe T
    • Journal Title

      Journal of Immunology

      Volume: 184 Pages: 6756-6765

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 生体部分肝移植における過小グラフト症候群に対するPGE1門脈注入療法の有用性の検討2010

    • Author(s)
      尾上隆司
    • Organizer
      第46回日本移植学会総会
    • Place of Presentation
      京都
    • Year and Date
      2010-10-21
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 肝類洞内皮細胞のアロ応答性T細胞制御能:in vivoモデルでの解明2010

    • Author(s)
      番匠谷将孝, 尾上隆司
    • Organizer
      第46回日本移植学会総会
    • Place of Presentation
      京都
    • Year and Date
      2010-10-21
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Advantageous effect of a continuous injection of PGE1 via the portal vein for small-for-size graft in adult-to-adult living donor liver transplantation2010

    • Author(s)
      尾上隆司
    • Organizer
      The 8th Japan-Korea Transplantation Forum
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-10-20
    • Related Report
      2010 Final Research Report
  • [Presentation] Advantageous effect of a continuous injection of PGE1 via the portal vein for small-for size graft in adult-to-adult living donor liver transplantation2010

    • Author(s)
      尾上隆司
    • Organizer
      The 8th Japan-Korea Transplantation Forum
    • Place of Presentation
      京都
    • Year and Date
      2010-10-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] 糖鎖抗原を表出した肝類洞内皮細胞はB細胞の抗体産生を抑制できる2010

    • Author(s)
      五十嵐友香, 尾上隆司
    • Organizer
      第28回日本肝移植研究会
    • Place of Presentation
      広島
    • Year and Date
      2010-07-02
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 肝類洞内皮細胞の免疫寛容誘導能の解析~肝移植後の免疫寛容をめざした試み2010

    • Author(s)
      番匠谷将孝, 尾上隆司
    • Organizer
      第28回日本肝移植研究会
    • Place of Presentation
      広島
    • Year and Date
      2010-07-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] ドナー肝由来活性化リンパ球移入を用いた肝移植後肝癌再発制御法の臨床評価2010

    • Author(s)
      尾上隆司
    • Organizer
      第46回日本肝臓学会総会
    • Place of Presentation
      山形
    • Year and Date
      2010-05-27
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 肝類洞内皮細胞の抗原特異的免疫寛容誘導能の解析2010

    • Author(s)
      番匠谷将孝, 尾上隆司
    • Organizer
      第46回日本肝臓学会総会
    • Place of Presentation
      山形
    • Year and Date
      2010-05-27
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Allogeneic Liver Sinusoidal Endothelial Cells Negatively Regulate the Immune Response of Corresponding T Cells in a Liver Endothelium Repopulation Model.2010

    • Author(s)
      Banshoudani M, Onoe T, et al.
    • Organizer
      American Transplant Congress 2010
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2010-05-01
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 肝類洞内皮細胞の抗原特異的免疫寛容誘導能~in vivoモデルでの解析~2010

    • Author(s)
      番匠谷将孝, 尾上隆司
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-04-08
    • Related Report
      2010 Final Research Report
  • [Presentation] 肝類洞内皮細胞の抗原特異的免疫寛容誘導能~ill vivoモデルでの解析~2010

    • Author(s)
      番匠谷将孝, 尾上隆司
    • Organizer
      第110回日本外科学会定期学術周回
    • Place of Presentation
      名古屋
    • Year and Date
      2010-04-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝類洞内皮細胞の抗原特異的免疫誘導能 -in vivo model での解析-2009

    • Author(s)
      番匠谷将孝
    • Organizer
      第45回 日本移植学会
    • Place of Presentation
      東京
    • Year and Date
      2009-09-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] LSEC tolerize allo-reactive T cells in a liver endothelium repopulation model.2009

    • Author(s)
      Banshoudani M, Onoe T, et al.
    • Organizer
      2009 European Society of Organ Transplantation
    • Place of Presentation
      Paris, France
    • Year and Date
      2009-08-30
    • Related Report
      2010 Final Research Report
  • [Presentation] LSEC tolerize allo-reactive T cells in a liver endothelium repopulation model2009

    • Author(s)
      番匠谷将孝
    • Organizer
      2009 European Society of Organ Transplantation
    • Place of Presentation
      仏・パリ
    • Year and Date
      2009-08-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] 当院における肝移植後の免疫寛容をめざした試み-肝類洞内皮細胞の抗原特異的免疫誘導能-2009

    • Author(s)
      番匠谷将孝
    • Organizer
      第27回 日本肝移植研究会
    • Place of Presentation
      三島
    • Year and Date
      2009-07-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Evidence for tolerizing allo reactive T cell by LSECs in a liver endothelium repopulation in vivo model.2009

    • Author(s)
      Banshoudani M, Onoe T, et al.
    • Organizer
      2009 American Transplantation Congress
    • Place of Presentation
      Boston, USA
    • Year and Date
      2009-05-30
    • Related Report
      2010 Final Research Report
  • [Presentation] Evidence for tolerizing allo reactive T cell by LSECs in a liver endothelium repopulation in vivo model2009

    • Author(s)
      番匠谷将孝
    • Organizer
      2009 American Transplantation Congress
    • Place of Presentation
      米・ボストン
    • Year and Date
      2009-05-30
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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

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