Synergistic effect of KRN7000 with interleukin-15, -7, and -2 on the expansion of human Vα24+Vβ11+ T cells in vitro

Nobusuke Nishi, Hans J J Van Der Vliet, Yasuhiko Koezuka, B. Mary E Von Blomberg, Rik J. Scheper, Herbert M. Pinedo, Giuseppe Giaccone

Research output: Contribution to journalArticlepeer-review

Abstract

KRN7000, (2S, 3S, 4R)-1-O-(α-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 Vα24 chain and a Vβ11 chain, was investigated using KRN7000, interleukin (IL)-15, IL-7, and IL-2 in vitro. KRN7000 stimulated the expansion of Vα24+Vβ11+ 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 Vα24+Vβ11+ T cells when combined with KRN7000. Intracellular expression of interferon (IFN)-γ and IL-4 in Vα24+Vβ11+ T cells expanded in the presence of KRN7000 was identified using flow cytometry. Vα24+Vβ11+ 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 Vα24+Vβ11+ 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. (C) American Society for Histocompatibility and Immunogenetics, 2000.

Original languageEnglish (US)
Pages (from-to)357-365
Number of pages9
JournalHuman Immunology
Volume61
Issue number4
DOIs
StatePublished - Apr 2000
Externally publishedYes

Keywords

  • α-Galactosylceramide
  • Granzyme B
  • Interleukin
  • NK T cell
  • Perforin

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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