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 journalArticle

60 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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