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Blood First Edition Paper, prepublished online November 6, 2009; DOI 10.1182/blood-2009-04-217729. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Watarai, H. Articles by Taniguchi, M. PubMed PubMed Citation Articles by Watarai, H. Articles by Taniguchi, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 22, 2009; accepted October 10, 2009. Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant V14-J18 TCR gene Hiroshi Watarai1, Andrei Rybouchkin2, Naomi Hongo1, Yuko Nagata1, Sakura Sakata1, Etsuko Sekine1, Nyambayar Dashtsoodol1, Takuya Tashiro1, Shin-ichiro Fujii3, Kanako Shimizu3, Kenji Mori1, Kyoko Masuda4, Hiroshi Kawamoto5, Haruhiko Koseki6 and Masaru Taniguchi1,3 1 Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; 2 Laboratory for Lymphocyte Cloning, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; 3 Laboratory for Cellular Immunotherapy, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; 4 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Tokyo, Japan; 5 Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; 6 Laboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan * Corresponding author; email: taniguti{at}rcai.riken.jp Abstract Establishment of a system with efficient generation of NKT cells from embryonic stem (ES) cells would enable us to identify the cells with NKT cell potential and obtain NKT cells with desired function. Here, by using cloned ES (NKT-ES) cells generated by the transfer of nuclei from mature NKT cells, we have established a culture system, which preferentially developed functional NKT cells, and also identified early NKT progenitors which first appeared on day 11 as a c-kit+ population in the co-cultures on OP9 cells with expression of Notch ligand, delta-like1 (OP9/Dll-1) and became c-kitlo/- on day 14. Interestingly, in the presence of Notch signals NKT-ES cells differentiated only to thymic CD44lo CD24hi NKT cells producing mainly IL-4, while NKT cells resemble to CD44hi CD24lo liver NKT cells producing mainly IFN- and exhibiting strong adjuvant activity in vivo were developed in the switch culture starting at day 14 in the absence of Notch. The cloned ES culture system offers a new opportunity for the elucidation of the molecular events on NKT cell development and for the establishment of NKT cell therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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