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

Autor: Nishi, N, van der Vliet, H J, Koezuka, Y, von Blomberg, B M, Scheper, R J, Pinedo, H M, Giaccone, G
Přispěvatelé: Medical oncology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, CCA - Cancer Treatment and quality of life, Pathology, AII - Cancer immunology
Jazyk: angličtina
Rok vydání: 2000
Zdroj: Human Immunology, 61(4), 357-65. Elsevier Inc.
Nishi, N, van der Vliet, H J, Koezuka, Y, von Blomberg, B M, Scheper, R J, Pinedo, H M & Giaccone, G 2000, ' 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 ', Human Immunology, vol. 61, no. 4, pp. 357-65 .
ISSN: 0198-8859
Popis: 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.
Databáze: OpenAIRE
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