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Development of a novel desensitization/immune-regulatory method by use of multi-potent suppressor B cells to induce immune-tolerance in allogeneic organ transplantation

Research Project

Project/Area Number 15H02555
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionHiroshima University

Principal Investigator

OHDAN Hideki  広島大学, 医歯薬保健学研究科(医), 教授 (10363061)

Co-Investigator(Kenkyū-buntansha) 小林 孝彰  愛知医科大学, 医学部, 教授 (70314010)
田中 友加  広島大学, 医歯薬保健学研究科(医), 准教授 (90432666)
尾上 隆司  独立行政法人国立病院機構(呉医療センター臨床研究部), 免疫応用科学研究室, 室長 (90549809)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000)
Fiscal Year 2017: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2016: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2015: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Keywords臓器移植 / 免疫寛容 / 脱感作 / B細胞 / 移植免疫 / 寛容誘導 / 拒絶反応
Outline of Final Research Achievements

B cells constitute a complex system of antigen-presenting cells (APCs) and exist as distinct subsets that differ in their lineage affiliation, surface molecule expression, and biological function, potentially regulating the immune response. In this study, we investigated the immune-regulatory roles of murine B cell subsets as regulatory APCs targeting alloreactive T cells. Anti-Balb/c T cell responses and serum levels of anti-Balb/c antibodies in the recipients of peritoneal cavity (PerC) B cells containing MHC class II+ CD80+ CD86+ PD-L1+ PD-L2+ cells were significantly lower than those in the recipients of splenic B cells. Pre-incubated with anti-PD-L1/PD-L2 mAbs prior to injection abrogated their immune-regulatory effects on anti-Balb/c T cells. The inoculation with Balb/c PerC B cells significantly prolonged the survival of subsequently grafted Balb/c hearts in B6 mouse recipients. Thus, the PerC PD-L1/PD-L2 B-1a cells suppress T cells responding to allostimulation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (15 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 8 results,  Invited: 5 results)

  • [Journal Article] PD-L1/PD-L2-expressing B-1 cells inhibit alloreactive T cells in mice2017

    • Author(s)
      Hirose T, Tanaka Y, Tanaka A, Sakai H, Sasaki Y, Shinohara N, Ohdan H
    • Journal Title

      PLoS One

      Volume: 12(6) Issue: 6 Pages: 1-16

    • DOI

      10.1371/journal.pone.0178765

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different sensitivities to calcineurin inhibitors between B cells responding to blood group A and B antigens2016

    • Author(s)
      Yamashita M, Tanaka Y, Tazawa H, Sakai H, Ohdan H.
    • Journal Title

      ISBT Science Series

      Volume: Volume 11, Issue Supplement S1 Issue: S1 Pages: 307-316

    • DOI

      10.1111/voxs.12233

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Different sensitivity of rituximab-treatment to B-cells between ABO-incompatible kidney and liver transplantation2016

    • Author(s)
      Hiroshi Morimoto, Kentaro Ide, Yuka Tanaka, Kohei Ishiyama, Masahiro Ohira, Hiroyuki Tahara, Tomonori Akita, Junko Tanaka, Hideki Ohdan
    • Journal Title

      Human Immunology

      Volume: 8859 Issue: 6 Pages: 30063-5

    • DOI

      10.1016/j.humimm.2016.04.013

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Role of Liver Sinusoidal Endothelial Cells in Induction of Carbohydrate Reactive B Cells Tolerance Through the Programmed Death 1/Programmed Death Ligand 1 Pathway2015

    • Author(s)
      Igarashi Y, Onoe T, Ohdan H.
    • Journal Title

      Transplantation

      Volume: 99(11) Issue: 11 Pages: 2325-2336

    • DOI

      10.1097/tp.0000000000000831

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] A novel role for MyD88 signaling downstream from toll-like receptors in B cells responding to blood group antigens2017

    • Author(s)
      Sakai H, Tanaka Y, Ohdan H.
    • Organizer
      American transplant congress 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PD-L1/PD-L2を発現したB細胞による免疫学的寛容誘導2017

    • Author(s)
      広瀬貴行, 田中友加, 田中飛鳥, 坂井寛, 篠原信雄, 大段秀樹
    • Organizer
      第53回日本移植学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Players of clinical tolerance: Tregs, Bregs, Macrophages, and others2016

    • Author(s)
      Ohdan H
    • Organizer
      Asian Transplantation Week 2016
    • Place of Presentation
      Incheon, Korea
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PD-L1/PD-L2-expressing B-1a cells inhibit allo-reactive T cells in mice2016

    • Author(s)
      Hirose T, Tanaka Y, Sakai S, Tanaka A, Sasaki Y, Ohdan H.
    • Organizer
      American Transplan Congress 2016
    • Place of Presentation
      Boston, USA
    • Year and Date
      2016-06-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct sensitivity of B-1a/B-1b/B-2 cell subpopulations to immunosuppressants2016

    • Author(s)
      Ohdan H
    • Organizer
      Transplantation Science Symposium Asian Regional Meetingb 2016
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2016-04-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] HLA抗体サブクラスと拒絶反応2016

    • Author(s)
      大段秀樹
    • Organizer
      第49回日本臨床腎移植学会
    • Place of Presentation
      鳥取
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Bacterial pathogens provoke B cells responding to blood group A-antigens to be resistant to calcineurin inhibitors through TLR -MyD88 pathway2015

    • Author(s)
      Sakai H, Tanaka Y, Ohdan H.
    • Organizer
      TSS2015 14th Transplantation Science Symposium
    • Place of Presentation
      Lorne, Australia
    • Year and Date
      2015-11-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of a Novel Tolerogenic B cell Subclass Co-expressing PD-L1/PD-L2 to Inhibit Allo-reactive T cells2015

    • Author(s)
      Hirose T, Tanaka Y, Sakai H, Tanaka A, Sasaki Y, Ohdan H
    • Organizer
      TSS2015 14th Transplantation Science Symposium
    • Place of Presentation
      Lorne, Australia
    • Year and Date
      2015-11-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FcγRの遺伝子多型が及ぼすリツキシマブB細胞抑制効果への影響2015

    • Author(s)
      坂井寛, 田中友加, 清水誠一, 井手健太郎, 広瀬貴行, 田中飛鳥, 矢野琢也, 佐伯吉弘, 谷峰直樹, 大平真裕, 田原裕之, 石山宏平, 尾上隆司, 田代裕尊, 大段秀樹.
    • Organizer
      第51回日本移植学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] New approaches for ABO-mismatched solid organ transplantation.2015

    • Author(s)
      Ohdan H.
    • Organizer
      ISBT 2015
    • Place of Presentation
      London, UK
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of Mouse Tolerogenic B cells Expressing PD-L1/PD-L2 in B-1a subset2015

    • Author(s)
      Hirose T, Tanaka Y, Sakai H, Sasaki Y, Ohdan H.
    • Organizer
      American Transplant Congress 2015
    • Place of Presentation
      Philadelphia, USA
    • Year and Date
      2015-05-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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