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Interleukin-27-dependent loss of CD4 T cell-memory during malaria infection

Research Project

Project/Area Number 16K08763
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Parasitology (including sanitary zoology)
Research InstitutionNagasaki University

Principal Investigator

KIMURA Daisuke  長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (50423637)

Research Collaborator YUI Katsuyuki  
YOSHIDA Hiroki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsマラリア / 免疫記憶 / 抑制 / T細胞 / IL-27 / 記憶CD4T細胞 / アポトーシス / 記憶B細胞 / 特異抗体 / CD4T細胞
Outline of Final Research Achievements

To examine the response of malaria-antigen specific CD4+ T cells, we used PbT-II mice that express TCR specific for the malaria antigen. C57BL/6 and Il27raKO mice were adoptively transferred with CD4+ T cells from PbT-II and Il27raKOPbT-II mice, respectively, infected with PbA and were cured by the drug treatment. One month later, Il27raKOPbT-II cells were maintained in Il27raKO mice and showed memory responses, while PbT-II cells almost disappeared from the spleen of C57BL/6 mice, confirming the effect of IL-27 on the survival of memory CD4+ T cells after malaria infection. When the mice were re-challenged with PbA, IL-27p28KO mice showed little parasitema, and their CD4+ T cells exhibited enhanced IFN-gamma response, while C57BL/6 mice exhibited high parasitemia levels. These results suggest that IL-27 inhibits the generation of memory CD4+ T cells by accelerating the apoptosis of parasite-specific CD4+ T cells during contraction phase of the immune response against PbA.

Academic Significance and Societal Importance of the Research Achievements

マラリアでは免疫記憶が成立しにくいことはよく知られており、マラリアに対する有効なワクチンがこれまでに開発されていない原因の1つでもある。しかしながら、そのメカニズムは未だによくわかっていなかった。本研究成果の「マラリア原虫特異的CD4T細胞がIL-27依存的にアポトーシスを引き起こす」は、これまで明らかにされていなかった免疫記憶抑制のメカニズムの1つであると考えられ、マラリアにおける免疫記憶抑制の解除法開発へつながるものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016

All Journal Article (2 results) Presentation (16 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] IL-27による免疫抑制2017

    • Author(s)
      吉田裕樹、木村大輔、由井克之
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 6 Pages: 23-29

    • Related Report
      2017 Research-status Report
  • [Journal Article] CLINICAL TOPICS:マラリア原虫感染とT細胞反応2017

    • Author(s)
      都田真奈、木村大輔
    • Journal Title

      別冊 BIO Clinica

      Volume: 6 Pages: 134-137

    • Related Report
      2017 Research-status Report
  • [Presentation] Interleukin-27-dependent loss of CD4+ T cell-memory during malaria infection2019

    • Author(s)
      木村大輔
    • Organizer
      第12回寄生虫感染免疫研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マラリア原虫感染におけるIL-27依存的記憶CD4T細胞消失2019

    • Author(s)
      木村大輔
    • Organizer
      第1回日本医学会連合Rising Starリトリート
    • Related Report
      2018 Annual Research Report
  • [Presentation] マラリア原虫治癒後における記憶CD4+T細胞の消失はIL-27依存的である2019

    • Author(s)
      木村大輔
    • Organizer
      第88回日本寄生虫学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Interleukin-27 regulates the generation of memory CD4+ T cells during malaria infection2018

    • Author(s)
      Daisuke Kimura
    • Organizer
      Sixth International Conference Ulaanbaatar, Mongolia. Current Advances in Microbiology and Immunology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Loss of memory CD4+ T-cells mediated by IL-27 during malaria infection2018

    • Author(s)
      Daisuke Kimura
    • Organizer
      第47回日本免疫学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Interleukin-27 dependent loss of memory CD4+ T-cells after malaria infection2018

    • Author(s)
      Daisuke Kimura, Mana Miyakoda, Odsuren Sukhbaatar, Sayuri Nakamae, Ganchimeg Bayarsaikhan, Kazumi Kimura, Hiromitsu Hara, Hiroki Yoshida, Katsuyuki Yui
    • Organizer
      第11回寄生虫感染免疫研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] マラリア原虫治癒後におけるIL-27依存的免疫記憶CD4+T細胞の消失2018

    • Author(s)
      木村大輔、都田真奈、Ganchimeg Bayarsaikhan、中前早百合、Odsuren Sukhbaatar、木村一美、原博満、吉田裕樹、由井克之
    • Organizer
      第87回日本寄生虫学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Interleukin-27 regulate the function CD4+ T cells during malaria infection2018

    • Author(s)
      Daisuke Kimura
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Interleukin-27 inhibits the generation of memory CD4+ T cells after recovery from malaria infection2017

    • Author(s)
      木村大輔
    • Organizer
      寄生虫感染免疫研究会
    • Place of Presentation
      徳島大学(徳島県・徳島市)
    • Year and Date
      2017-02-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Interleukin-27 inhibits the generation of memory CD4+ T cells after treatment with anti-malarial drug2017

    • Author(s)
      Daisuke Kimura
    • Organizer
      The 13th Nagasaki-Singapore Medical Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] マラリア原虫治癒後における免疫記憶消失はIL-27依存的である2017

    • Author(s)
      木村大輔、都田真奈、Akbari Masoud、木村一美、原博満、吉田裕樹、由井克之
    • Organizer
      第86回日本寄生虫学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] nterleukin-27 inhibits the generation of memory CD4+ T cells during malaria infection2017

    • Author(s)
      Daisuke Kimura, Mana Miyakoda, Ganchimeg Bayarsaikhan, Sayuri Nakamae, Odsuren Sukhbaatar, Kazumi Kimura, Hiromitsu Hara, Hiroki Yoshida, Katsuyuki Yui
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Interleukin-27-dependent loss of CD4+ T cell-memory during malaria infection2017

    • Author(s)
      Daisuke Kimura, Mana Miyakoda, Ganchimeg Bayarsaikhan, Sayuri Nakamae, Odsuren Sukhbaatar, Kazumi Kimura, Hiromitsu Hara, Hiroki Yoshida, Katsuyuki Yui
    • Organizer
      第46回日本免疫学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Interleukin-27 inhibits the generation of memory CD4+ T cells against malaria infection2016

    • Author(s)
      木村大輔
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県・宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] マラリア原虫治癒後におけるIL-27依存的免疫記憶の消失2016

    • Author(s)
      木村大輔
    • Organizer
      日本寄生虫学会南日本支部大会
    • Place of Presentation
      佐賀大学(佐賀県・佐賀市)
    • Year and Date
      2016-11-05
    • Related Report
      2016 Research-status Report
  • [Presentation] マラリア原虫感染後におけるIL-27依存的な免疫記憶の抑制2016

    • Author(s)
      木村大輔
    • Organizer
      日本インターフェロン・サイトカイン学会
    • Place of Presentation
      長崎大学(長崎県・長崎市)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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