title: Polarization of Valpha24+ Vbeta11+ natural killer T cells of healthy volunteers and cancer patients using alpha-galactosylceramide-loaded and environmentally instructed dendritic cells.
abstract: CD1d-restricted natural killer T (NKT) cells play important regulatory roles in various immune responses. NKT cell-derived T helper (Th) 1 cytokines are important in the induction of antitumor immune responses in mice. Because the CD1d-restricted Valpha24(+) Vbeta11(+) NKT cell population in cancer patients is decreased both in size and in its capacity to secrete IFN-gamma, therapeutic strategies based on reconstitution of type 1 polarized Valpha24(+) Vbeta11(+) NKT cells merit additional investigation. Here, we report the simultaneous strong expansion and type 1 polarization of human invariant Valpha24(+) Vbeta11(+) NKT cells using alpha-galactosylceramide-loaded type 1 dendritic cells and interleukin 15. Type 1 polarized Valpha24(+) Vbeta11(+) NKT cells produced high levels of IFN-gamma, tumor necrosis factor alpha, and granulocyte macrophage colony-stimulating factor, and induced strong cytotoxicity in Jurkat cells in an alpha-galactosylceramide-dependent manner. Importantly, the cytokine profile of Valpha24(+) Vbeta11(+) NKT cells that were initially expanded under Th2 polarizing conditions could be reversed to a Th1 cytokine profile, indicating the plasticity of the cytokine profile of the human adult Valpha24(+) Vbeta11(+) NKT cell population.
authors.affiliation: Department of Medical Oncology, Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands.
authors.forename: Hans J J
authors.initials: HJ
authors.lastname: van der Vliet
authors.forename: Johan W
authors.initials: JW
authors.lastname: Molling
authors.forename: Nobusuke
authors.initials: N
authors.lastname: Nishi
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Masterson
authors.forename: Wendy
authors.initials: W
authors.lastname: Kölgen
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: Herbert M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005699:Galactosylceramides / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D018418:Th2 Cells / Q000276:immunology
chemical_list: D015703:Antigens, CD; D005699:Galactosylceramides; D019409:Interleukin-15; D018664:Interleukin-12