Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Vα14-Jα18 TCRα gene
Autor: | Andrei Rybouchkin, Haruhiko Koseki, Masaru Taniguchi, Yuko Nagata, Nyambayar Dashtsoodol, Hiroshi Kawamoto, Takuya Tashiro, Etsuko Sekine, Hiroshi Watarai, Sakura Sakata, Shin-ichiro Fujii, Kanako Shimizu, Kyoko Masuda, Naomi Hongo, Kenji Mori |
---|---|
Rok vydání: | 2010 |
Předmět: |
Nuclear Transfer Techniques
Time Factors Receptors Antigen T-Cell alpha-beta Immunology Population CD1 chemical and pharmacologic phenomena Biology Biochemistry Interferon-gamma Mice Animals Progenitor cell education Gene Cells Cultured Embryonic Stem Cells Cell Nucleus Mice Knockout Mice Inbred ICR education.field_of_study Receptors Notch Calcium-Binding Proteins CD24 Antigen Cell Differentiation hemic and immune systems Cell Biology Hematology Natural killer T cell Embryonic stem cell In vitro Cell biology Hyaluronan Receptors Intercellular Signaling Peptides and Proteins Natural Killer T-Cells Interleukin-4 Stem cell |
Zdroj: | Blood. 115:230-237 |
ISSN: | 1528-0020 0006-4971 |
Popis: | 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-kitlo/− on day 14. Interestingly, in the presence of Notch signals, NKT-ES cells differentiated only to thymic CD44lo CD24hi NKT cells producing mainly interleukin-4 (IL-4), whereas NKT cells resembling CD44hi CD24lo liver NKT cells producing mainly interferon γ (IFN-γ) 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. |
Databáze: | OpenAIRE |
Externí odkaz: |