Mechanisms of regulatory T-cell control of humoral immunity

• Project/Area Number: 25860356
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: WING James 大阪大学, 免疫学フロンティア研究センター, 特任助教 (00648694)
• Co-Investigator(Renkei-kenkyūsha): SAKAGUCHI Shimon 大阪大学, 免疫学フロンティア研究センター, 教授 (30280770) ; KUROSAKI Tomohiro 大阪大学, 免疫学フロンティア研究センター, 特任教授 (50178125) ; ISE Wataru 大阪大学, 免疫学フロンティア研究センター, 特任准教授 (70323483)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Regulatory T-cells / T follicular helper / Vaccination / Antibody response / T Follicular helper / Antibody responses / 制御性T細胞 / 免疫制御

Outline of Final Research Achievements

I discovered that Tregs control the formation of Tfh and resulting B-cell germinal center reactions via the suppressive molecule CTLA-4. This is achieved by depletion of the costimulatory molecules CD80 and CD86 from the surface of antigen presenting B-cells and dendritic cells which are critical for the formation of Tfh. Since Tfh are vital for the production of high quality antibody responses and B-cell memory this means that Treg are able to control the production of antibody via CTLA-4.

Research Products

• [Journal Article] In vivo induction of T-follicular helper cells by modulation of regulatory T cell function. (2015)
  • Author(s): Wing , JB. Sakaguchi, S.
  • Journal Title: Methods in molecular biology. Volume: 1291 Pages: 77-85
  • DOI: 10.1007/978-1-4939-2498-1_7
  • ISBN: 9781493924974, 9781493924981
  • Peer Reviewed
• [Journal Article] Regulatory T cells control antigen-specific expansion of Tfh cell number and humoral immune responses via the coreceptor CTLA-4. (2014)
  • Author(s): Wing, JB. Ise, W. Kurosaki, T. Sakaguchi, S.
  • Journal Title: Immunity Volume: 41 Issue: 6 Pages: 1013-25
  • DOI: 10.1016/j.immuni.2014.12.006
  • Peer Reviewed / Open Access
• [Journal Article] Detection of self-reactive CD8⁺ T cells with an anergic phenotype in healthy individuals. (2014)
  • Author(s): Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M, Saito T, Nishioka M, Wing JB, Adeegbe D, Katayama I, Sakaguchi S.
  • Journal Title: Science Volume: 346 Issue: 6216 Pages: 1536-40
  • DOI: 10.1126/science.aaa1292
  • Peer Reviewed
• [Journal Article] Autosomal dominant immune dysregulation syndrome in humans with CTLA-4 mutations. (2014)
  • Author(s): Schubert D, et al.
  • Journal Title: Nature Med. Volume: 20 Issue: 12 Pages: 1410-1416
  • DOI: 10.1038/nm.3746
  • Peer Reviewed
• [Journal Article] Foxp3⁺ T(reg) cells in humoral immunity. (2014)
  • Author(s): Wing JB, Sakaguchi S.
  • Journal Title: Int Immunol. Volume: 26(2) Issue: 2 Pages: 61-9
  • DOI: 10.1093/intimm/dxt060
  • Peer Reviewed
• [Presentation] Regulatory T-cells control antigen-specific Tfh expansion and humoral immune responses via CTLA-4 (2015)
  • Author(s): Wing, JB. Ise, W. Kurosaki, T. Sakaguchi, S.
  • Organizer: Keystone Symposium: T Cells: Regulation and Effector Function (D3)
  • Place of Presentation: Snowbird Resort, Snowbird, Utah USA
  • Year and Date: 2015-03-29 – 2015-04-02
• [Presentation] Regulatory T-cells control antigen-specific Tfh expansion and humoral immune responses via CTLA-4 (2014)
  • Author(s): Wing, JB. Ise, W. Kurosaki, T. Sakaguchi, S.
  • Organizer: The 43rd Annual Meeting of the Japanease Society for Immunology
  • Place of Presentation: Kyoto International Conference Center, Japan
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Regulatory T-cells control antigen-specific Tfh expansion and humoral immune responses via CTLA-4 (2014)
  • Author(s): Wing, JB. Ise, W. Kurosaki, T. Sakaguchi, S.
  • Organizer: The Fourth International Conference on Regulatory T Cells and Th Subsets and Clinical Application in Human Diseases
  • Place of Presentation: Renaissance Hotel, Shanghai, China
  • Year and Date: 2014-11-01 – 2014-11-04
• [Presentation] Regulatory T-cells control antigen-specific Tfh expansion and humoral immune responses via CTLA-4 (2014)
  • Author(s): Wing, JB. Ise, W. Kurosaki, T. Sakaguchi, S.
  • Organizer: The 13th Awaji International Forum on Infection and Immunity in Nara
  • Place of Presentation: Nara Prefectural New Public Hall, Japan
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] Regulatory T-cells modulate T-follicular helper and germinal center formation via CTLA-4 (2013)
  • Author(s): Wing JB, Ise W, Kurosaki T, Sakaguchi S.
  • Organizer: Kyoto T Cell Conference 2013
  • Place of Presentation: Shiran Kaikan, Kyoto University, Kyoto
• [Presentation] Regulatory T-cells modulate T-follicular helper and germinal center formation via CTLA-4 (2013)
  • Author(s): Wing JB, Ise W, Kurosaki T, Sakaguchi S.
  • Organizer: Gordon research conference T Follicular Helper Cells: Basic Discoveries and Clinical Applications
  • Place of Presentation: The Chinese University of Hong Kong, Hong Kong, China
• [Presentation] Regulatory T-cells modulate T-follicular helper and germinal center formation via CTLA-4 (2013)
  • Author(s): Wing JB, Ise W, Kurosaki T, Sakaguchi S.
  • Organizer: Annual meeting of Japanese society for Immunology
  • Place of Presentation: Makuhari Messe, Chiba.
• [Book] 臨床免疫・アレルギー科: 制御性 T 細胞によるTfh細胞および胚中心形成制御機構 (2015)
  • Author(s): Wing JB, Morita T, Sakaguchi S.
  • Total Pages: 92
  • Publisher: 科学評論社
• [Remarks] IFReC Significant achievements
  • URL: http://www.ifrec.osaka-u.ac.jp/en/research/20141219_1.htm
• [Remarks] http://www.ifrec.osaka-u.ac.jp/index-e.php