title: Effective stimulation of invariant natural killer T cells by oligomannose-coated liposomes.
abstract: vThe in vitro and in vivo response of invariant natural killer T (iNKT) cells to alpha-galactosylceramide (αGC)-containing oligomannose-coated liposomes (αGC-OMLs) was examined to determine whether selective delivery of αGC to dendritic cells (DCs) and subsequent activation of iNKT cells could be achieved. Splenocytes stimulated with αGC-OMLs produced higher levels of IFN-γ compared to those stimulated with bare liposomes without an oligomannose coating (αGC-BLs). The ratio of IFN-γ/IL-4 produced from αGC-OML-treated splenocytes was higher than those produced from αGC-BL- and soluble αGC-treated cells. Depletion of CD3(+)-, DX5(+)- or CD11c(+)-cells from splenocytes almost completely abolished the αGC-OML-stimulated cytokine production, suggesting that both NKT cells and DCs were involved in the response to αGC-OML stimulation. In addition, αGC-OMLs were incorporated into both splenic and bone marrow-derived DCs more effectively than αGC-BLs. iNKT cells stimulated with DCs with ingested αGC-OMLs produced much higher levels of IFN-γ than those stimulated with DCs containing αGC-BLs or soluble αGC. Systemic administration of αGC-OMLs led to modification of the kinetics of IFN-γ production in vivo and also resulted in predominant production of IFN-γ from splenocytes over IL-4. In addition, iNKT cells proliferated and expanded upon in vivo activation of the cells with αGC-OMLs much more extensively than with αGC-BLs or soluble αGC. Collectively, our results suggest that αGC-OMLs can be used as a preferential delivery system for lipid antigens to DCs to activate iNKT cells in vivo and ex vivo.
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishii
authors.forename: Naoya
authors.initials: N
authors.lastname: Kojima
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014312:Trisaccharides / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D005699:Galactosylceramides; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014312:Trisaccharides; C493154:alpha-galactosylceramide; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; C023872:mannotriose; D007371:Interferon-gamma