title: Alternative pathway for the development of Vα14+NKT cells directly from CD4-CD8-thymocytes that bypasses the CD4+CD8+stage.
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.
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.|Core Research Laboratory, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia.
authors.forename: Nyambayar
authors.initials: N
authors.lastname: Dashtsoodol
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Tomokuni
authors.initials: T
authors.lastname: Shigeura
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Aihara
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ozawa
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kojo
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Michishige
authors.initials: M
authors.lastname: Harada
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Takaho A
authors.identifier: 0000-0002-2801-2463
authors.initials: TA
authors.lastname: Endo
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D060168:Thymocytes / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta