Ikarashi Yoshinori, Iizuka Akira, Heike Yuji, Yoshida Mitsuzi, Takaue Yoichi, Wakasugi Hiro
Pharmacology Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Immunol Lett. 2005 Nov 15;101(2):160-7. doi: 10.1016/j.imlet.2005.05.007.
Mouse natural killer T cells with invariant Valpha14 rearrangement (Valpha14i NKT cells) can rapidly produce both Th1 and Th2 cytokines and regulate various immune responses, such as autoimmunity and tumor immunity. In this study, we describe the phenotypical and functional characterization of in vitro-expanded mouse Valpha14i NKT cells from spleen using a combination of alpha-galactosylceramide (alpha-GalCer) and IL-2. The expanded Valpha14i NKT cells retained the memory/activated (CD44(+)CD69(+)CD62L(-)) and CD4(+) or CD4(-)8(-) double negative phenotypes but modulated or lost the classical NKT cell marker, NK1.1. The expanded Valpha14i NKT cells continuously released IL-4 and IFNgamma and induced NK cell IFNgamma production in vitro. Furthermore, the expanded Valpha14i NKT cells migrated into the liver and spleen after adoptive transfer into lymphopenic SCID mice, and they were able to rapidly produce IL-4 and IFNgamma after alpha-GalCer injection. Our findings suggest that the intrinsic characteristics of the cytokine secretion of Valpha14i NKT cells were equivalent to that of in vitro-expanded Valpha14i NKT cells. In vitro-expanded Valpha14i NKT cells are considered to be useful for NKT cell defect-related diseases, such as autoimmunity and cancer.
具有恒定Vα14重排的小鼠自然杀伤T细胞（Vα14i NKT细胞）能够快速产生Th1和Th2细胞因子，并调节各种免疫反应，如自身免疫和肿瘤免疫。在本研究中，我们描述了使用α-半乳糖神经酰胺（α-GalCer）和白细胞介素-2组合在体外扩增的来自脾脏的小鼠Vα14i NKT细胞的表型和功能特征。扩增后的Vα14i NKT细胞保留了记忆/活化（CD44(+)CD69(+)CD62L(-)）以及CD4(+)或CD4(-)8(-)双阴性表型，但调节或丧失了经典的NKT细胞标志物NK1.1。扩增后的Vα14i NKT细胞持续释放白细胞介素-4和干扰素γ，并在体外诱导自然杀伤细胞产生干扰素γ。此外，将扩增后的Vα14i NKT细胞过继转移到淋巴细胞减少的重症联合免疫缺陷（SCID）小鼠体内后，它们迁移至肝脏和脾脏，并且在注射α-GalCer后能够快速产生白细胞介素-4和干扰素γ。我们的研究结果表明，Vα14i NKT细胞细胞因子分泌的内在特性与体外扩增的Vα14i NKT细胞相当。体外扩增的Vα14i NKT细胞被认为对与NKT细胞缺陷相关的疾病，如自身免疫和癌症有用。
