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

KRN7000, (2S, 3S, 4R)-1-O-(alpha-D-galactop-yranosyl)-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 V alpha 24 chain and a V beta 11 chain, was investigated using KRN7000, interleukin (IL)-15, IL-7, and IL-2 in vitro. KRN7000 stimulated the expansion of V alpha 24(+)V beta 11(+) 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 V alpha 24(+)V beta 11(+) T cells when combined with KRN7000. Intracellular expression of interferon (IFN)-gamma and IL-4 in V alpha 24(+)V beta 11(+) T cells expanded in the presence of KRN7000 was identified using flow cytometry. V alpha 24(+)V beta 11(+) 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 V alpha 24(+)V beta 11(+) 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. Published by Elsevier Science Inc.