使用负载α-半乳糖神经酰胺和环境诱导的树突状细胞对健康志愿者和癌症患者的Valpha24 + Vbeta11 + 自然杀伤T细胞进行极化
Polarization of Valpha24+ Vbeta11+ natural killer T cells of healthy volunteers and cancer patients using alpha-galactosylceramide-loaded and environmentally instructed dendritic cells.
作者信息
van der Vliet Hans J J, Molling Johan W, Nishi Nobusuke, Masterson Allan J, Kölgen Wendy, Porcelli Steven A, van den Eertwegh Alfons J M, von Blomberg B Mary E, Pinedo Herbert M, Giaccone Giuseppe, Scheper Rik J
机构信息
Department of Medical Oncology, Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands.
出版信息
Cancer Res. 2003 Jul 15;63(14):4101-6.
CD1d-restricted natural killer T (NKT) cells play important regulatory roles in various immune responses. NKT cell-derived T helper (Th) 1 cytokines are important in the induction of antitumor immune responses in mice. Because the CD1d-restricted Valpha24(+) Vbeta11(+) NKT cell population in cancer patients is decreased both in size and in its capacity to secrete IFN-gamma, therapeutic strategies based on reconstitution of type 1 polarized Valpha24(+) Vbeta11(+) NKT cells merit additional investigation. Here, we report the simultaneous strong expansion and type 1 polarization of human invariant Valpha24(+) Vbeta11(+) NKT cells using alpha-galactosylceramide-loaded type 1 dendritic cells and interleukin 15. Type 1 polarized Valpha24(+) Vbeta11(+) NKT cells produced high levels of IFN-gamma, tumor necrosis factor alpha, and granulocyte macrophage colony-stimulating factor, and induced strong cytotoxicity in Jurkat cells in an alpha-galactosylceramide-dependent manner. Importantly, the cytokine profile of Valpha24(+) Vbeta11(+) NKT cells that were initially expanded under Th2 polarizing conditions could be reversed to a Th1 cytokine profile, indicating the plasticity of the cytokine profile of the human adult Valpha24(+) Vbeta11(+) NKT cell population.
CD1d限制性自然杀伤T(NKT)细胞在多种免疫反应中发挥重要的调节作用。NKT细胞衍生的辅助性T(Th)1细胞因子在诱导小鼠抗肿瘤免疫反应中起重要作用。由于癌症患者中CD1d限制性的Vα24(+)Vβ11(+)NKT细胞群体在数量和分泌干扰素-γ的能力上均有所下降,基于重建1型极化的Vα24(+)Vβ11(+)NKT细胞的治疗策略值得进一步研究。在此,我们报告了使用负载α-半乳糖神经酰胺的1型树突状细胞和白细胞介素15可使人不变的Vα24(+)Vβ11(+)NKT细胞同时实现强力扩增和1型极化。1型极化的Vα24(+)Vβ11(+)NKT细胞产生高水平的干扰素-γ、肿瘤坏死因子α和粒细胞巨噬细胞集落刺激因子,并以α-半乳糖神经酰胺依赖的方式在Jurkat细胞中诱导强烈的细胞毒性。重要的是,最初在Th2极化条件下扩增的Vα24(+)Vβ11(+)NKT细胞的细胞因子谱可逆转至Th1细胞因子谱,这表明成人Vα24(+)Vβ11(+)NKT细胞群体的细胞因子谱具有可塑性。