Polarization of Vα24+ Vβ11+ natural killer T cells of healthy volunteers and cancer patients using α-galactosylceramide-loaded and environmentally instructed dendritic cells

Hans J J Van der Vliet, Johan W. Molling, Nobusuke Nishi, Allan J. Masterson, Wendy Kölgen, Steven A. Porcelli, Alfons J M Van den Eertwegh, B. Mary E Von Blomberg, Herbert M. Pinedo, Giuseppe Giaccone, Rik J. Scheper

Research output: Contribution to journalArticlepeer-review

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 Vα24+ Vβ11+ NKT cell population in cancer patients is decreased both in size and in its capacity to secrete IFN-γ, therapeutic strategies based on reconstitution of type 1 polarized Vα24+ Vβ11+ NKT cells merit additional investigation. Here, we report the simultaneous strong expansion and type 1 polarization of human invariant Vα24+ Vβ11+ NKT cells using α-galactosylceramide-loaded type 1 dendritic cells and interleukin 15. Type 1 polarized Vα24+ Vβ11+ NKT cells produced high levels of IFN-γ, tumor necrosis factor α, and granulocyte macrophage colony-stimulating factor, and induced strong cytotoxicity in Jurkat cells in an α-galactosylceramide-dependent manner. Importantly, the cytokine profile of Vα24+ Vβ11+ NKT cells that were initially expanded under Th2 polarizing conditions could be reversed to a Thl cytokine profile, indicating the plasticity of the cytokine profile of the human adult Vα24+ Vβ11+ NKT cell population.

Original languageEnglish (US)
Pages (from-to)4101-4106
Number of pages6
JournalCancer Research
Volume63
Issue number14
StatePublished - Jul 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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