Polarization of Valpha24+ Vbeta11+ natural killer T cells of healthy volunteers and cancer patients using alpha-galactosylceramide-loaded and environmentally instructed dendritic cells.
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.
van der Vliet
Hans J J
HJ
Department of Medical Oncology, Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands.
Molling
Johan W
JW
Nishi
Nobusuke
N
Masterson
Allan J
AJ
Kölgen
Wendy
W
Porcelli
Steven A
SA
van den Eertwegh
Alfons J M
AJ
von Blomberg
B Mary E
BM
Pinedo
Herbert M
HM
Giaccone
Giuseppe
G
Scheper
Rik J
RJ
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
D015703:Antigens, CD; D005699:Galactosylceramides; D019409:Interleukin-15; D018664:Interleukin-12