Alternative pathway for the development of Vα 14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+ CD8+ stage

Nyambayar Dashtsoodol, Tomokuni Shigeura, Minako Aihara, Ritsuko Ozawa, Satoshi Kojo, Michishige Harada, Takaho A. Endo, Takashi Watanabe, Osamu Ohara, Masaru Taniguchi

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27 Citations (Scopus)

Abstract

Although invariant V α 14 + natural killer T cells (NKT cells) are thought to be generated from CD4 + CD8 + double-positive (DP) thymocytes, the developmental origin of CD4 - CD8 - double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (T H 1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage. These findings provide new insight into understanding of the development of NKT cells and propose a role for timing of expression of the invariant T cell antigen receptor in determining the functional properties of NKT cells.

Original languageEnglish
Pages (from-to)274-282
Number of pages9
JournalNature Immunology
Volume18
Issue number3
DOIs
Publication statusPublished - Feb 15 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Dashtsoodol, N., Shigeura, T., Aihara, M., Ozawa, R., Kojo, S., Harada, M., Endo, T. A., Watanabe, T., Ohara, O., & Taniguchi, M. (2017). Alternative pathway for the development of Vα 14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+ CD8+ stage. Nature Immunology, 18(3), 274-282. https://doi.org/10.1038/ni.3668