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

• DOI: 10.1038/ni.3668
• Publication Date: 2017-01-30T18:02:58Z
• Authors: Nyambayar Dashtso...; Tomokuni Shigeura; Minako Aihara; Ritsuko Ozawa; Satoshi Kojo; Michishige Harada; Takaho A Endo; Takashi Watanabe; Osamu Ohara; Masaru Taniguchi
• Keywords: Cytotoxicity, Immunologic; Mice, Knockout; 0303 health sciences; Thymocytes; CD8 Antigens; Receptors, Antigen, T-Cell, alpha-beta; Cell Differentiation; Th1 Cells; Immunity, Innate; DNA-Binding Proteins; Mice, Inbred C57BL; Mice; 03 medical and health sciences; CD4 Antigens; Animals; Cytokines; Natural Killer T-Cells; Cell Lineage; Cells, Cultured

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.