Polarization of Valpha24+ Vbeta11+ natural killer T cells of healthy volunteers and cancer patients using alpha-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 journalArticleAcademicpeer-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 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.

Original languageEnglish
Pages (from-to)4101-6
Number of pages6
JournalCancer Research
Volume63
Issue number14
Publication statusPublished - 15 Jul 2003

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