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Formation and maintenance of long-lived memory T helper cells

Research Project

Project/Area Number 20K22764
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0803:Pathology, infection/immunology, and related fields
Research InstitutionTottori University

Principal Investigator

TOKOYODA Koji  鳥取大学, 医学部, 教授 (20362402)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsヘルパーT細胞 / 免疫記憶 / 長寿命 / 骨髄
Outline of Research at the Start

一部の免疫細胞は抗原の刺激を受けた後、記憶細胞として長寿命を獲得し維持される。しかし、どのように免疫細胞が長寿命を獲得し維持されるのか、細胞内外の分子メカニズムは不明な点が多い。応募者は今まで、記憶ヘルパーT細胞の形成において、過剰な細胞分裂を経て形成されることやサイトカインIL-2が必要であることを示してきた。また新たに記憶ヘルパーT細胞の維持においては、解糖系に依存することや接着分子からのシグナルが必要なことを見出している。本研究では、長寿命の獲得や維持に必須な候補分子のin vivoでの機能を解明し、記憶ヘルパーT細胞の長寿命の獲得や維持に関与する分子メカニズムの全体像を明らかにする。

Outline of Final Research Achievements

Some CD4 T cells can be maintained as memory T helper cells for long periods after antigenic stimulation. However, ir remains unclear how memory T helper cells are generated and maintained. In this study, we have investigated the molecular mechanisms utilizing retrovirus-induced shRNA, neutralization antibodies and knock-out mice. We here show that enhanced cell division and IL-2Rb expression are essential for the generation of memroy T helper cells and that CXCR6 expression, glycolysis and Focal adhesion kinase are required for their maintenance. These results contribute to the understanding of cellular and molecular mechanisms on the generation and maintenance of memory T helper cells, totally on immune memory.

Academic Significance and Societal Importance of the Research Achievements

免疫記憶、特にその中枢で働く記憶ヘルパーT細胞の形成や維持の分子メカニズムを知ることは、どのように我々が感染した病原体を記憶しているのかという学術的疑問を解決することにつながる。さらにどのように記憶が形成され維持されているかがわかれば、ワクチンの最大の目的である免疫記憶は、どのように誘導すれば最も効率が良いのかという新しい指標になる。さらにアレルギーや自己免疫疾患の慢性化の原因も免疫記憶であるため、いかに病原性の記憶細胞を除去するのか、その標的分子を明らかにすることにも貢献する。

Report

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

    (9 results)

All 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] DRFZ Berlin(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] B lymphocytes and plasma cells as drivers of rheumatic diseases2022

    • Author(s)
      Hiepe F, Alexander T, Dorner T, Hauser AE, Hoyer BF, Kubagawa H, Skriner K, Tokoyoda K
    • Journal Title

      Zeitschrift fur Rheumatologie

      Volume: 5 Issue: 8 Pages: 1-7

    • DOI

      10.1007/s00393-022-01189-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Homeostasis and Durability of T-Cell Memory?The Resting and the Restless T-Cell Memory2021

    • Author(s)
      Radbruch A, McGrath MA, Siracusa F, Hoffmann U, Sercan-Alp O, Hutloff A, Tokoyoda K, Chang HD, Dong J
    • Journal Title

      Cold Spring Harbor Perspectives in Biology

      Volume: 13 Issue: 7 Pages: a038083-a038083

    • DOI

      10.1101/cshperspect.a038083

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Stromal Cell-Contact Dependent PI3K and APRIL Induced NF-κB Signaling Prevent Mitochondrial- and ER Stress Induced Death of Memory Plasma Cells2020

    • Author(s)
      Cornelis Rebecca、Hahne Stefanie、Taddeo Adriano、Petkau Georg、Malko Darya、Durek Pawel、Thiem Manja、Heiberger Lukas、Peter Lena、Mohr Elodie、Klaeden Cora、Tokoyoda Koji、Siracusa Francesco、Hoyer Bimba Franziska、Hiepe Falk、Mashreghi Mir-Farzin、Melchers Fritz、Chang Hyun-Dong、Radbruch Andreas
    • Journal Title

      Cell Reports

      Volume: 32 Issue: 5 Pages: 107982-107982

    • DOI

      10.1016/j.celrep.2020.107982

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple developmental pathways lead to the generation of CD4 T-cell memory2020

    • Author(s)
      Hojyo Shintaro、Tumes Damon、Murata Akihiko、Tokoyoda Koji
    • Journal Title

      International Immunology

      Volume: 32 Issue: 9 Pages: 589-595

    • DOI

      10.1093/intimm/dxaa051

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Isotype-specific metabolic requirements for survival of bone marrow plasma cells2021

    • Author(s)
      Murata A, Sasaki H, Tokoyoda K
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Bone marrow and splenic memory CD4 T cells are differently maintained in terms of cytokine signals, cell adhesion and cellular metabolism2021

    • Author(s)
      Kimura U, Mursell M, Nagano S, Tokoyoda K
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Antigen priming of conventional dendritic cell 1 preferentially guides the differentiation of resting memory CD4 T cells2021

    • Author(s)
      Matsuo K, Hojyo S, Yoshino M, Tokoyoda K
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Salmonella escapes from immune memory2021

    • Author(s)
      Koji Tokoyoda
    • Organizer
      5th International Immunological Memory and Vaccine Forum Symposium
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2020-09-29   Modified: 2023-01-30  

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