krn-7000 and Leukemia

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Cell Communication; Cell Transplantation; Child; Dendritic Cells; Female; Galactosylceramides; Humans; Interferon-gamma; Killer Cells, Natural; Leukemia; Lymphocyte Activation; Male; Mice; Mice, Inbred Strains; Middle Aged; Young Adult