胸腺ダブルネガティブ前駆細胞からのＮＫＴ細胞新規分化経路の解明

2015 Fiscal Year Annual Research Report

• Project/Area Number: 24790490
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: D NYAMBAYAR 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (50443057)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: NKT / CD1d / thymus / development

Outline of Annual Research Achievements

Although it is widely believed that invariant Vα14 NKT cells are generated from CD4+CD8+ double-positive thymocytes by selection on CD1d, a process termed the DP pathway, it is still not fully understood whether NKT cells develop exclusively by the DP pathway in a manner closely resembling that of conventional αβ T cells, or some alternatives to this pathway exist. Here we provide genetic evidence supporting the presence of an alternative developmental pathway of NKT cells from late CD4-CD8- double-negative stage thymocytes without passing DP pathway, where the DP-specific ablation of Rag2 resulted in a loss of Vα14Jα18 rearrangement by DP cells suggesting mature NKT cells developed in this mouse were generated from DN thymocytes with intact expressions of both Rag2 and Vα14Jα18 transcripts. Moreover, fate-mapping approach by introducing DP-specific E8III-Cre transgene into Rosa26YFP reporter mice, where a reporter gene expression labels progenies of DP precursors, allowed detecting NKT cells without expression of YFP reporter demonstrating these cells were differentiated through the DN pathway without passing the DP stage. Furthermore, NKT cells generated by DN pathway show characteristics of Th1-biased cytotoxic effector cells suggesting this developmental pathway gives rise preferentially to Th1-type NKT cells. Our present findings provide new insights in understanding the development of NKT cells in the thymus, which seems to be different from that of conventional αβ T cells.

Research Products

• [Journal Article] Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire. (2016)
  • Author(s): Nyambayar Dashtsoodol, Tomokuni Shigeura, Ritsuko Ozawa, Michishige Harada, Satoshi Kojo, Takashi Watanabe, Haruhiko Koseki, Manabu Nakayama, Osamu Ohara, Masaru Taniguchi.
  • Journal Title: PLoS One. Volume: 11 Pages: 1-10
  • DOI: 10.1371/journal.pone.0153347
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Discovery of NKT cells and development of NKT cell-targeted anti-tumor immunotherapy. (2015)
  • Author(s): Masaru Taniguchi, Michishige Harada, Nyambayar Dashtsoodol, Satoshi Kojo.
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci. Volume: 91 Pages: 292-304
  • DOI: 10.2183/pjab.91.292
  • Peer Reviewed / Open Access
• [Presentation] A validation of the requirement for Vα14 NKT cells for tumor rejection using newly generated Traj18-deficient mice with undisturbed T cell receptor repertoire. (2015)
  • Author(s): Dashtsoodol N, Shigeura T, Watanabe T, Harada M, Kojo S, Endo T, Ohara O, Koseki H, Taniguchi M.
  • Organizer: CD1-MR1 2015
  • Place of Presentation: Mantra Lorne, Victoria, Australia
  • Year and Date: 2015-11-15 – 2015-11-19
  • Int'l Joint Research
• [Remarks] 統合生命医科学研究センター 免疫制御戦略研究グループ 研究紹介
  • URL: http://www.riken.jp/research/labs/ims/immune_reg/