Heterogeneity of naive CD4 T cells

• Project/Area Number: 25670227
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: TOKUHISA Takeshi 千葉大学, 学長 (20134364)
• Co-Investigator(Kenkyū-buntansha): SAKAMOTO Akemi 千葉大学, 大学院医学研究院, 助教 (90359597)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 免疫学 / 発生・分化 / 遺伝子 / 濾胞ヘルパーＴ細胞 / 胸腺 / 記憶Ｔ細胞

Outline of Final Research Achievements

We found Ly6C high (Ly6Chi) and low (Ly6Clo) naive CD4 T cells in the spleen of a mouse strain. Ly6Chi but not Ly6Clo naive CD4 T cells produced IFN-g, TNF-a and IL-2 after activation with anti-CD3 and anti-CD28 Abs. Within 2 d after leaving thymus, 50% of CD4+CD8- thymocytes which express low levels of Ly6C stably up-regulate Ly6C without cell division in the spleen. Moreover, majority of naive CD4 T cells in the spleen of Bcl6-deficient mice belonged to Ly6Chi naive CD4 T cells. When CD4+CD8- thymocytes were stimulated with IFN-a or IFN-g but not with IL-2 in vitro, Ly6Chi naive CD4 T cells were developed within 2 d and CD4+CD8- thymocytes from Bcl6-KO mice were more sensitive to IFN-a or IFN-g stimulation. These data indicate that Bcl6 regulates heterogeneity of naive CD4 T cells in the periphery by controlling the signals initiated by IFN-a or IFN-g stimulation.

Research Products

• [Journal Article] DA-Raf-dependent inhibition of the Ras-ERK signaling pathway in type 2 alveolar epithelial cells controls alveolar formation. (2014)
  • Author(s): Watanabe-Takano H, Takano K, Sakamoto A, Matsumoto K, Tokuhisa T, Endo T, Hatano M.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Issue: 22
  • DOI: 10.1073/pnas.1321574111
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells. (2014)
  • Author(s): Ikari J, Inamine A, Yamamoto T, Watanabe-Takano H, Yoshid a N, Fujimura L, Taniguchi T, Sakamoto A, Hatano M, Tatsumi K, Tokuhisa T, Arima M.
  • Journal Title: Allergy. Volume: 69 Issue: 2 Pages: 223-230
  • DOI: 10.1111/all.12328
  • Peer Reviewed / Open Access
• [Journal Article] Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production (2013)
  • Author(s): Okada K, Ueshima S, Kawao N, Yano M, Tamura Y, Tanaka M, Sakamoto A, Hatano M, Arima M, Miyata S, Nagai N, Tokuhisa T, and Matsuo O
  • Journal Title: Life Sci Volume: 93 Issue: 2-3 Pages: 89-95
  • DOI: 10.1016/j.lfs.2013.05.023
  • Peer Reviewed
• [Journal Article] ADAR1 induces adenosine-targeted DNA mutations in senescent Bcl6-deficient cells (2013)
  • Author(s): Tsuruoka, N., Arima, M., Yoshida, N., Okada, S., Sakamoto, A., Hatano, M., Satake, H., Arguni, E., Wang, J.-Y., Yang, J.-H., Nishikura, K., Sekiya, S., Shozu, M. and Tokuhisa, T.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 2 Pages: 826-836
  • DOI: 10.1074/jbc.m112.365718
  • Peer Reviewed
• [Presentation] 肝臓における薬物代謝の性差を制御する新規分子の探索 (2015)
  • Author(s): 紙谷 聡英、近田裕美、井田絹代、坂本明美、徳久剛史.
  • Organizer: 第8回日本性差医学・医療学会学術集会
  • Place of Presentation: ホテルクレメント徳島（徳島）
  • Year and Date: 2015-01-31 – 2015-02-01
• [Presentation] Role of enteric neurons in regulation of intestinal epithelial homeostasis. (2014)
  • Author(s): Fujimura L, Ohara Y, Arima M, Sakamoto A, Tokuhisa T, Hatano M.
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都国際会議場（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 粘液記憶細胞の形成と維持 (2014)
  • Author(s): 徳久剛史
  • Organizer: 東京免疫フォーラム
  • Place of Presentation: 東京大学医科学研究（東京）
  • Invited
• [Remarks] 千葉大学大学院医学研究院 分化制御学
  • URL: http://www.m.chiba-u.ac.jp/class/devgen/