Abstract
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 language | English |
---|---|
Pages (from-to) | 357-65 |
Number of pages | 9 |
Journal | Human immunology |
Volume | 61 |
Issue number | 4 |
Publication status | Published - Apr 2000 |
Keywords
- 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