Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Vα14 NKT cells
Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Vα14 NKT cells
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DOI：
10.1073/pnas.95.10.5690
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发表时间：
1998-05-12
影响因子：
11.1
通讯作者：
Taniguchi, M
中科院分区：
文献类型：
--
作者：
Kawano, T;Cui, JQ;Taniguchi, M
我们最近已经确定α-半乳糖神经酰胺（α-GalCer）作为一种特异性配体的一个不变的V α 14/V β 8.2 T细胞受体上唯一表达的大多数V α 14 NKT细胞，一种新的淋巴细胞亚群。在这里，我们报告了α-GalCer选择性激活V α 14 NKT细胞，从而预防肿瘤转移。配体激活的V α 14 NKT细胞的效应机制似乎是由自然杀伤（NK）样非特异性细胞毒性介导的。实际上，通过加入冷靶肿瘤细胞或通过用抑制穿孔素的活化和分泌的康卡霉素A1处理，而不是通过针对参与NKT细胞识别和常规细胞毒性的分子（例如CD 1d、V β 8、NK1.1、Ly 49 C、Fas）的mAb，降低了由α-GalCer活化的V α 14 NKT细胞获得的细胞毒性指数。这些结果表明，配体激活的V α 14 NKT细胞通过CD 1d/V α 14 T细胞受体非依赖性NK样机制直接杀伤肿瘤细胞。
We have recently identified alpha-galactosylceramide (alpha-GalCer) as a specific ligand for an invariant V alpha 14/V beta 8.2 T cell receptor exclusively expressed on the majority of V alpha 14 NKT cells, a novel subset of lymphocytes. Here, we report that alpha-GalCer selectively activates V alpha 14 NKT cells resulting in prevention of tumor metastasis, The effector mechanisms of the ligand-activated V alpha 14 NKT cells seem to be mediated by natural killer (NK)-like nonspecific cytotoxicity. Indeed, the cytotoxic index obtained by alpha-GalCer-activated V alpha 14 NKT cells was reduced by the addition of cold target tumor cells or by treatment with concanamycin Al which inhibits activation and secretion of perforin, but not by mAbs against molecules involved in the NKT cell recognition and conventional cytotoxicity, such as CD1d, V beta 8, NK1.1, Ly49C, Fas. or Fas ligand, These results suggest that the ligand-activated V alpha 14 NKT cells kill tumor cells directly through a CD1d/V alpha 14 T cell receptor-independent, NK-like mechanism.