Synergistic effect of KRN7000 with interleukin-15, -7, and -2 on the expansion of human V alpha 24+V beta 11+ T cells in vitro

N Nishi, H J van der Vliet, Y Koezuka, B M von Blomberg, R J Scheper, H M Pinedo, G Giaccone

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KRN7000, (2S, 3S, 4R)-1-O-(alpha-D-galactopyranosyl)-2-(N-hexacosanoylamino)-1, 3, 4-octadecanetriol, has been shown to prevent tumor metastasis to the liver through the activation of natural killer (NK) T cells in mice. In this study, the proliferation of human NK T cells, which express an invariant T cell antigen receptor (TCR) consisting of a Valpha24 chain and a Vbeta11 chain, was investigated using KRN7000, interleukin (IL)-15, IL-7, and IL-2 in vitro. KRN7000 stimulated the expansion of Valpha24(+)Vbeta11(+) T cells derived from peripheral blood mononuclear cells in a dose-dependent fashion, with some fluctuation between donors. IL-15, IL-7, and IL-2 synergistically stimulated the expansion of Valpha24(+)Vbeta11(+) T cells when combined with KRN7000. Intracellular expression of interferon (IFN)-gamma and IL-4 in Valpha24(+)Vbeta11(+) T cells expanded in the presence of KRN7000 was identified using flow cytometry. Valpha24(+)Vbeta11(+) T cells, expanded in the presence of KRN7000, contained granzyme (Gr) B-positive granules and perforin-positive granules. The addition of IL-15 to the culture containing KRN7000 increased GrB expression in Valpha24(+)Vbeta11(+) T cells while IL-7 and IL-2 failed to do it. In conclusion, the antitumor effect of KRN7000 may depend, in part, on granule-mediated cell killing through the activation of NK T cells and IL-15 may potentiate this effect.

Original languageEnglish
Pages (from-to)357-65
Number of pages9
JournalHuman immunology
Issue number4
Publication statusPublished - Apr 2000


  • Adjuvants, Immunologic/pharmacology
  • Cells, Cultured
  • Drug Synergism
  • Galactosylceramides/immunology
  • Granzymes
  • Humans
  • Interferon-gamma/biosynthesis
  • Interleukin-15/physiology
  • Interleukin-2/physiology
  • Interleukin-4/biosynthesis
  • Interleukin-7/physiology
  • Interleukins/physiology
  • Killer Cells, Natural/immunology
  • Lymphocyte Activation/drug effects
  • Membrane Glycoproteins/biosynthesis
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell, alpha-beta/biosynthesis
  • Serine Endopeptidases/biosynthesis
  • T-Lymphocyte Subsets/drug effects

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