title: Human leukemic cells loaded with alpha-galactosylceramide (alpha-GalCer) activate murine NKT cells in situ.
abstract: 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.
authors.affiliation: 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.
authors.forename: Kanako
authors.initials: K
authors.lastname: Shimizu
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hidaka
authors.forename: Kara
authors.initials: K
authors.lastname: Bickham
authors.forename: Mina
authors.initials: M
authors.lastname: Moriwaki
authors.forename: Koji
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Kawano
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002450:Cell Communication / Q000276:immunology; D017690:Cell Transplantation; D002648:Child; D003713:Dendritic Cells / Q000378:metabolism / Q000637:transplantation; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects*; D007938:Leukemia / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D055815:Young Adult
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma