Abstract
Establishment of a system with efficient generation of natural killer T (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, using cloned ES (NKT-ES) cells generated by the transfer of nuclei from mature NKT cells, we have established a culture system that preferentially developed functional NKT cells and also identified early NKT progenitors, which first appeared on day 11 as a c-kit(+) population in the cocultures on OP9 cells with expression of Notch ligand, delta-like1 (OP9/Dll-1) and became c-kit(lo/-) on day 14. Interestingly, in the presence of Notch signals, NKT-ES cells differentiated only to thymic CD44(lo) CD24(hi) NKT cells producing mainly interleukin-4 (IL-4), whereas NKT cells resembling CD44(hi) CD24(lo) liver NKT cells producing mainly interferon gamma (IFN-gamma) 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD24 Antigen / immunology
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CD24 Antigen / metabolism
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Calcium-Binding Proteins
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Cell Differentiation / immunology*
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Cell Nucleus / immunology*
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Cell Nucleus / metabolism
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Cells, Cultured
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / immunology*
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Embryonic Stem Cells / metabolism
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Hyaluronan Receptors / immunology
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Hyaluronan Receptors / metabolism
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Intercellular Signaling Peptides and Proteins / immunology
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Intercellular Signaling Peptides and Proteins / metabolism
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-4 / immunology
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Interleukin-4 / metabolism
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Mice
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Mice, Inbred ICR
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Mice, Knockout
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Natural Killer T-Cells / cytology
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Natural Killer T-Cells / immunology*
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Natural Killer T-Cells / metabolism
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Nuclear Transfer Techniques
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Receptors, Antigen, T-Cell, alpha-beta / immunology*
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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Receptors, Notch / immunology
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Receptors, Notch / metabolism
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Time Factors
Substances
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CD24 Antigen
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Calcium-Binding Proteins
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Dlk1 protein, mouse
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Hyaluronan Receptors
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Intercellular Signaling Peptides and Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Notch
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Interleukin-4
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Interferon-gamma