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Nat Immunol. 2017 Mar;18(3):274-282. doi: 10.1038/ni.3668. Epub 2017 Jan 30.

Alternative pathway for the development of Vα14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+CD8+ stage.

Author information

1
Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
2
Core Research Laboratory, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia.
3
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Abstract

Although invariant Vα14+ 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 (TH1)-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.

PMID:
28135253
DOI:
10.1038/ni.3668
[Indexed for MEDLINE]

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