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Roles of memory T helper cells in bone marrow and spleen

Research Project

Project/Area Number 21K07081
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionTottori University

Principal Investigator

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

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords免疫記憶 / ヘルパーT細胞 / 骨髄 / 二次応答 / T細胞 / 免疫 / ニッチ
Outline of Research at the Start

二次免疫応答において、記憶ヘルパーT細胞の動態や機能、役割は不明な点が多い。全身性の免疫応答では、記憶ヘルパーT細胞が主に骨髄に、また一部は脾臓に維持され、末梢血やリンパ節など他組織には維持されていない。応募者は記憶ヘルパーT細胞を特異的に除去することを可能にしており、記憶ヘルパーT細胞の動態や機能、役割を解析できるようになっている。本研究では、記憶ヘルパーT細胞を血清学的かつ遺伝学的に除去し、各々の動態や機能、役割を明らかにする。

Outline of Final Research Achievements

In this study, we serologically and genetically depleted memory helper T cells in the bone marrow and spleen, and aimed to clarify their dynamics, functions, and roles. During the secondary response, bone marrow memory helper T cells expressed activation markers and functional molecules such as CD40L within 4 hours, whereas splenic memory helper T cells did not show activation until 24 hours later. Furthermore, the rapid migration from bone marrow to the periphery and interaction with B cells in the bone marrow were observed at the same time, indicating that bone marrow memory helper T cells are mainly involved in the secondary response.

Academic Significance and Societal Importance of the Research Achievements

本研究により、骨髄で維持される記憶ヘルパーT細胞が高い機能をもち、主に二次応答で貢献していることが分かった。ワクチンなどで記憶ヘルパーT細胞の形成を指標にする際は、骨髄を観察する必要があることが分かったとともに、自己免疫疾患やアレルギー疾患などでも主として働く記憶ヘルパーT細胞を除去するためには、骨髄の記憶ヘルパーT細胞を除く必要があることが分かった。この発見は、ワクチン開発や疾患の治療法確立のために、大きく役立つものであり、学術的にも社会的にも大きく意義がある。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (17 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (1 results)

  • [Int'l Joint Research] Deutsches Rheumaforschungszentrum(ドイツ)

    • Related Report
      2022 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
      2022 Research-status Report 2021 Research-status 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 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Targeting Isotype-Specific Plasma Cell Niches2023

    • Author(s)
      常世田好司
    • Organizer
      30th Annual Henry Kunkel Society Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Maintenance of memory lymphocytes2023

    • Author(s)
      常世田好司
    • Organizer
      第52回日本免疫学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 免疫記憶とアレルギーの寛解2023

    • Author(s)
      常世田好司
    • Organizer
      第52回日本アレルギー学会中四国支部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Salmonella evades from humoral immunity and antibiotics2023

    • Author(s)
      木村宇輝、常世田好司
    • Organizer
      第52回日本免疫学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Memory T helper cell differentiation regulated by a type 1 conventional dendritic cell subpopulation2023

    • Author(s)
      大木こころ、常世田好司
    • Organizer
      第52回日本免疫学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Macrophages function as survival niches for CD4+ skin-resident memory T cells2023

    • Author(s)
      村田暁彦、常世田好司
    • Organizer
      第52回日本免疫学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Transport of skin-specific self-antigen by XCR1-positive dermal dendritic cells2023

    • Author(s)
      吉野三也、常世田好司
    • Organizer
      第52回日本免疫学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Generation of autoreactive bone marrow plasma cells2023

    • Author(s)
      岡田航、常世田好司
    • Organizer
      第52回日本免疫学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Regulatory T cell-dependent maintenance of memory T helper cells in vivo2022

    • Author(s)
      Sano Nagano, Uki Kimura, Mei Sakagami, Koji Tokoyoda
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] cDC1-dependent generation of memory CD4 T cells2022

    • Author(s)
      Kana Matsuo, Ohki Kokoro, Koji Tokoyoda
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Isotype-specific metabolic requirements for survival of bone marrow plasma cells2021

    • Author(s)
      Akihiko Murata, Harumi Sasaki, Koji Tokoyoda
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Research-status 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)
      Uki Kimura, Mathias Mursell, Sano Nagano, Koji Tokoyoda
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Antigen priming of conventional dendritic cell 1 preferentially guides the differentiation of resting memory CD4 T cells2021

    • Author(s)
      Kana Matsuo, Shintaro Hojyo, Miya Yoshino, Koji Tokoyoda
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Research-status Report
  • [Book] 基礎から学ぶ免疫学2023

    • Author(s)
      山下政克/編 常世田好司 他/著
    • Total Pages
      288
    • Publisher
      羊土社
    • ISBN
      9784758121682
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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