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Role of positive selection in the functional development of T cells

Research Project

Project/Area Number 24790475
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionThe University of Tokushima

Principal Investigator

TAKADA Kensuke  徳島大学, 疾患プロテオゲノム研究センター, 講師 (40570073)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords獲得免疫 / T細胞 / 正の選択 / 胸腺 / 免疫学
Research Abstract

beta5t-containing thymoproteasomes expressed in cortical thymic epithelial cells (cTECs) are essential for positive selection of CD8 T cells. In this study, we characterized monoclonal CD8 T cells that were selected in the absence of beta5t. We found that OT-I CD8 T cells generated in beta5t-deficient mice were hyperresponsive to SIINFEKL antigen and its variants. In the periphery, CD8 T cells generated in beta5t-deficient mice were enriched with CD44hiCD122hi memory-phenotype depending on IL-2/15 receptor signals, suggesting that beta5t-dependent positive selection is required for homeostatic maintenance of CD8 T cells. In response to infection with Listeria monocytogenes expressing ovalbumin, OT-I CD8 T cells from beta5t-deficient mice preferentially differentiated into short-lived effector cells. These results indicate that the positive selection in the thymus not only determines TCR recognition specificity but also preconditions antigen responsiveness of CD8 T cells.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (21 results)

All 2014 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (15 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Gimap3 and Gimap5 cooperate to maintain T-cell numbers in the mouse.2014

    • Author(s)
      Yano K, Carter C, Yoshida N, Abe T, Yamada A, Nitta T, Ishimaru N, Takada K, Butcher GW, Takahama Y.
    • Journal Title

      Eur J Immunol

      Volume: 44 Issue: 2 Pages: 561-572

    • DOI

      10.1016/j.bbrc.2014.05.023

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gimap3 and Gimap5 cooperate to maintain T-cell numbers in the mouse2014

    • Author(s)
      Yano K, Carter C, Yoshida N, Abe T, Yamada A, Nitta T, Ishimaru N, Takada K, Butcher GW, Takahama Y.
    • Journal Title

      Eur J Immunol

      Volume: 44 Issue: 2 Pages: 561-572

    • DOI

      10.1002/eji.201343750

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development and function of thymic cortical epithelial cells.2014

    • Author(s)
      Takada K, Ohigashi I, Kasai M, Nakase H, Takahama Y.
    • Journal Title

      Curr Top Microbiol Immunol

      Volume: 373 Pages: 1-17

    • DOI

      10.1007/82_2013_322

    • ISBN
      9783642402517, 9783642402524
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Beta5t-containing thymoproteasome : specific expression in thymic cortical epithelial cells and role in positive selection of CD8+ T cells2012

    • Author(s)
      Takahama Y
    • Journal Title

      Current Opinion in Immunology

      Volume: 24 Issue: 1 Pages: 92-98

    • DOI

      10.1016/j.coi.2012.01.006

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] What is the positive selection for?2014

    • Author(s)
      Takada K. and Takahama Y
    • Organizer
      The 3rd Bizan Immunology Symposium
    • Place of Presentation
      The University of Tokushima, Tokushima, Japan
    • Year and Date
      2014-02-02
    • Related Report
      2013 Final Research Report
  • [Presentation] What is the positive selection for?2014

    • Author(s)
      Takada, K. and Takahama, Y.
    • Organizer
      The 3rd Bizan Immunology Symposium
    • Place of Presentation
      徳島大学藤井節郎記念医科学センター(徳島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional conditioning of CD8 T cells by thymoproteasome - dependent positive selection2013

    • Author(s)
      Takada K. and Takahama Y
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉県幕張メッセ
    • Year and Date
      2013-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional conditioning of CD8 T cells by thymoproteasome - dependent positive selection2013

    • Author(s)
      Takada K. and Takahama Y
    • Organizer
      The 6th International Workshop of Kyoto T Cell Conference
    • Place of Presentation
      Kyoto University, Kyoto, Japan
    • Year and Date
      2013-07-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional conditioning of CD8 T cells by thymoproteasome - dependent positive selection2013

    • Author(s)
      Takada K. and Takahama Y
    • Organizer
      Functional conditioning of CD8 T cells by thymoproteasome-dependent positive selection
    • Place of Presentation
      Convention Center, Honolulu, USA
    • Year and Date
      2013-05-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Thymoproteasome dependent positive selection conditions cytokine reactivity of mature CD8 T cells2013

    • Author(s)
      5. Takada K. and Takahama Y
    • Organizer
      Bizan Immunology Symposium"Immune System Development, Deviation, and Regulation"
    • Place of Presentation
      University of Tokushima, Tokushima, Japan
    • Year and Date
      2013-01-25
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional conditioning of CD8 T cells by thymoproteasome-dependent positive selection.2013

    • Author(s)
      Takada, K. and Takahama, Y.
    • Organizer
      第42回 日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional conditioning of CD8 T cells by thymoproteasome-dependent positive selection.2013

    • Author(s)
      Takada, K. and Takahama, Y.
    • Organizer
      The 6th International Workshop of Kyoto T Cell Conference
    • Place of Presentation
      京都大学芝蘭会館(京都府)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional conditioning of CD8 T cells by thymoproteasome-dependent positive selection.2013

    • Author(s)
      Takada, K. and Takahama, Y.
    • Organizer
      The 100th American Association of Immunologists Annual Meeting.
    • Place of Presentation
      Hawaii Convention Center (Honolulu, USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] B5t欠損マウスにおける末梢CD8T細胞の解析2012

    • Author(s)
      6.高田健介、高浜洋介
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      兵庫県国際会議場
    • Year and Date
      2012-12-07
    • Related Report
      2013 Final Research Report
  • [Presentation] B5t欠損マウスにおける末梢CD8T細胞の機能異常2012

    • Author(s)
      7.高田健介、高浜洋介
    • Organizer
      第21回Kyoto T Cell Conference
    • Place of Presentation
      京都府京都大学
    • Year and Date
      2012-07-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional abnormality of peripheral CD8 T cells in B 5t deficient mice2012

    • Author(s)
      8. Takada K. and Takahama Y
    • Organizer
      The 99th American Association of Immunologists Annual Meeting
    • Place of Presentation
      Hynes Convention Center, Boston, USA
    • Year and Date
      2012-05-06
    • Related Report
      2013 Final Research Report
  • [Presentation] β5t欠損マウスにおける末梢CD8T細胞の解析2012

    • Author(s)
      高田健介、高浜洋介
    • Organizer
      第41回 日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Presentation] β5t欠損マウスにおける末梢CD8T細胞の機能異常2012

    • Author(s)
      高田健介、高浜洋介
    • Organizer
      第21回 Kyoto T Cell Conference
    • Place of Presentation
      京都大学(京都府)
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional abnormality of peripheral CD8 T cells in β5t-deficient mice.2012

    • Author(s)
      Kensuke Takada, Yousuke Takahama
    • Organizer
      The 99th American Association of Immunologists Annual Meeting
    • Place of Presentation
      Hynes Convention Center (Boston, USA)
    • Related Report
      2012 Research-status Report
  • [Book] 最新内科学 総論8章1-3 「獲得免疫」2012

    • Author(s)
      高田健介、高浜洋介
    • Total Pages
      6
    • Publisher
      西村書店
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.genome.tokushimau.ac.jp/dei

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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