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Identifying a novel self-reactive T cell subpopulation and its functional significance

Research Project

Project/Area Number 20K16272
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49070:Immunology-related
Research InstitutionTohoku University

Principal Investigator

Kawabe Takeshi  東北大学, 医学系研究科, 准教授 (50834652)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsCD4 T細胞 / 恒常性 / 感染免疫 / 自己免疫疾患 / T細胞
Outline of Research at the Start

T細胞は獲得免疫反応に必須のリンパ球である。申請者は最近、CD4 T細胞の一分画に「メモリー表現型(MP)細胞」を同定し、抗原認識非依存的かつサイトカイン依存的に感染防御に寄与するという極めて特異な自然免疫機能を発見した。MP細胞は自己抗原認識依存的にナイーブ前駆細胞より産生されることから、同細胞はある種の炎症環境下等において自己免疫疾患を誘発する可能性がある。そこで本研究では、MP細胞の産生・維持・分化・活性化機構を明らかにするとともに、同細胞による自己免疫疾患発症機構を解明する。本研究により、これまで難病とされてきた自己免疫疾患の病態解明や根治的治療法の確立が期待される。

Outline of Final Research Achievements

CD4 T lymphocytes are essential for useful adaptive immune responses. Among CD4 T cells, we have recently identified a subpopulation with a memory phenotype that arises from naive precursors dependently of self antigen recognition and can exert innate immune function in infectious conditions. Based on this finding, this study aimed to define markers for this subpopulation and unravel its host-protective as well as autoimmune functions. In this study, we identified three markers that specify MP versus foreign antigen-specific memory cells. Moreover, we found that MP cells contain a Th1-like “MP1" subset and this subpopulation can exert innate effector function. Furthermore, we are obtaining evidence arguing that MP cells can induce systemic inflammation in certain circumstances. Together our results suggest MP cells as a unique CD4 T cell subpopulation possessing innate effector function as well as autoimmune potential.

Academic Significance and Societal Importance of the Research Achievements

従来、T細胞は外来抗原特異的獲得免疫応答にのみ寄与するものとされてきたが、本研究により、その一部の細胞集団「MP細胞」が自然免疫的様式にて感染防御に寄与することが明らかになった。本研究成果は、従来の古典的T細胞免疫学の理解に一石を投じるものである。今後、MP細胞の自然免疫機能や炎症惹起能を細胞・分子レベルで解明することにより、新規抗感染症治療戦略の提唱や自己免疫・炎症性疾患に対する根治的治療法の創出にも結び付くものと期待される。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (18 results)

All 2022 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Memory-phenotype CD4+ T cells: a naturally arising T lymphocyte population possessing innate immune function.2022

    • Author(s)
      Kawabe T, Sher A.
    • Journal Title

      Int Immunol

      Volume: 34 Issue: 4 Pages: 189-196

    • DOI

      10.1093/intimm/dxab108

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Homeostasis of naive and memory T lymphocytes.2021

    • Author(s)
      Kawabe T, Yi J, Sprent J.
    • Journal Title

      Cold Spring Harb Perspect Biol

      Volume: 13 Issue: 9 Pages: a037879-a037879

    • DOI

      10.1101/cshperspect.a037879

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] GITR controls intestinal inflammation by suppressing IL-15-dependent NK cell activity.2020

    • Author(s)
      Sakurai T, Okuyama Y, Kobayashi S, Phung HT, Asao A, Kawabe T, Ndhlovu LC, Riccardi C, Kudo H, Wada M, Nio M, So T, Ishii N.
    • Journal Title

      FASEB J.

      Volume: 34(11) Issue: 11 Pages: 14820-14831

    • DOI

      10.1096/fj.202001675r

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Germ-free conditions modulate host purine metabolism, exacerbating adenine-induced kidney damage.2020

    • Author(s)
      Mishima E, Ishijo M, Kawabe T, Kikuchi K, Akiyama Y, Toyohara T, Suzuki C, Asao A, Ishii N, Fukuda S, Abe T
    • Journal Title

      Toxins

      Volume: 12 Issue: 9 Pages: 547-547

    • DOI

      10.3390/toxins12090547

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state.2020

    • Author(s)
      Kawabe T, Yi J, Kawajiri A, Hilligan K, Fang D, Ishii N, Yamane H, Zhu J, Jankovic D, Kim KS, Trinchieri G, Sher A
    • Journal Title

      Nat Commun

      Volume: 11 Issue: 1 Pages: 3366-3366

    • DOI

      10.1038/s41467-020-17136-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 'Rinse and Replace': Boosting T Cell Turnover To Reduce HIV-1 Reservoirs.2020

    • Author(s)
      Grossman Z, Singh NJ, Simonetti FR, Lederman MM, Douek DC, Deeks SG, Contributing authors (Full authorship: Kawabe T, Bocharov G, Meier-Schellersheim M, Alon H, Chomont N, Grossman Z, Sousa AE, Margolis L, Maldarelli F)
    • Journal Title

      Trends Immunol

      Volume: 41 Issue: 6 Pages: 466-480

    • DOI

      10.1016/j.it.2020.04.003

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells2020

    • Author(s)
      Phung Hai The、Nagashima Hiroyuki、Kobayashi Shuhei、Asano Naoki、Machiyama Tomoaki、Sakurai Tsuyoshi、Tayama Shun-ichi、Asao Atsuko、Imatani Akira、Kawabe Takeshi、Okuyama Yuko、Ishii Naoto、So Takanori
    • Journal Title

      ImmunoHorizons

      Volume: 4 Issue: 3 Pages: 129-139

    • DOI

      10.4049/immunohorizons.2000007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] New insights on T-cell self-tolerance.2020

    • Author(s)
      Yi J, Kawabe T, Sprent J.
    • Journal Title

      Curr Opin Immunol

      Volume: 63 Pages: 14-20

    • DOI

      10.1016/j.coi.2019.10.002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IQ motif-containing GTPase-activating protein 1 is essential for the optimal maintenance of lung ILC2s2019

    • Author(s)
      Tayama Shunichi、Okuyama Yuko、Phung Hai The、Asao Atsuko、Kobayashi Shuhei、Musha Tomomi、Machiyama Tomoaki、Sakurai Tsuyoshi、Zhang Chengming、Ushio-Fukai Masuko、Kawabe Takeshi、So Takanori、Ishii Naoto
    • Journal Title

      International Immunology

      Volume: - Issue: 4 Pages: 233-241

    • DOI

      10.1093/intimm/dxz077

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] IL-12 derived from type 1 dendritic cells tonically promotes the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes in steady state.2021

    • Author(s)
      Kawabe T, Yi J, Kawajiri A, Hilligan K, Fang D, Ishii N, Yamane H, Zhu J, Jankovic D, Kim KS, Trinchieri G, Sher A.
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Inflammatory potential of self-driven memory-phenotype CD4+ T cells.2021

    • Author(s)
      Kawajiri A, Ishii M, Li J, Yang Z, Sato K, Tayama S, Okuyama Y, Harigae H, Ishii N, Kawabe T.
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Reactive sulfide species generated by cysteinyl-tRNA synthetase plays a regulatory role in T cell-induced colitis in a T cell-intrinsic manner.2021

    • Author(s)
      Tayama S, Kawabe T, Kitamura Y, Hiraide K, Li J, Yang Z, Kawajiri A, Sato K, Okuyama Y, Morita M, Akaike T, Ishii N.
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規Tリンパ球「MP細胞」の恒常性維持機構の解明ならびにその自己免疫活性の究明.2021

    • Author(s)
      河部 剛史
    • Organizer
      第8回JCRベーシックリサーチカンファレンス
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 新たなCD4 T細胞「MP細胞」の産生・分化機構とその病理学的機能の解明.2021

    • Author(s)
      河部 剛史
    • Organizer
      第49回日本臨床免疫学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Differentiation of a novel memory-phenotype CD4+ T lymphocyte population and its immunological significance2020

    • Author(s)
      Takeshi Kawabe
    • Organizer
      第49回日本免疫学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] IL-12 derived from type 1 dendritic cells tonically promotes the differentiation of innate T-bet(high) memory-phenotype CD4+ T lymphocytes in steady state2020

    • Author(s)
      Takeshi Kawabe
    • Organizer
      Cytokines 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] IL-12 derived from CD8a+ dendritic cells drives the differentiation of innate-like T-bet(high) memory-phenotype CD4+ T lymphocytes in steady state2020

    • Author(s)
      Takeshi Kawabe
    • Organizer
      Immunology 2020 (cancelled due to COVID-19)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] IQ motif-containing GTPase-activating protein 1 is essential for the optimal maintenance of lung ILC2s2020

    • Author(s)
      Shunichi Tayama
    • Organizer
      Immunology 2020 (cancelled due to COVID-19)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2023-01-30  

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