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Int J Hematol. 2010 Jul;92(1):152-60. doi: 10.1007/s12185-010-0616-7. Epub 2010 Jun 16.

Human leukemic cells loaded with alpha-galactosylceramide (alpha-GalCer) activate murine NKT cells in situ.

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Research Unit for Cellular Immunotherapy and Research Unit for Therapeutic Model, Institute of Physical and Chemical Research (RIKEN), Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.


Invariant NKT cells (NKT) cells become activated after stimulation with antigen-presenting cells (APCs) loaded with the NKT cell ligand, alpha-galactosylceramide (alpha-GalCer). In this study, we investigated whether human APCs loaded with alpha-GalCer have the ability to activate NKT cells in mice. We found that human dendritic cells (DCs) loaded with alpha-GalCer (hDC/Gal) and injected into C57BL/6 mice stimulated the secretion of IFN-gamma by activated murine NKT cells. Furthermore, the number of transferred hDC/Gal correlated with the number of recovered IFN-gamma-producing spleen cells, indicating that the capacity of APCs to load alpha-GalCer can be measured by IFN-gamma release in an ELISPOT assay. Finally, alpha-GalCer-loaded human leukemic cell lines and primary leukemic cells injected into C57BL/6 mice also had the capacity to stimulate murine NKT cells in vivo. These results indicate that in vivo murine NKT cell responses can be used to quantitate the alpha-GalCer-loading capacity of human APCs. This method could be utilized to develop future immunotherapies in which NKT cells are targeted for activation.

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