Chamoto Kenji, Takeshima Tsuguhide, Kosaka Akemi, Tsuji Takemasa, Matsuzaki Junko, Togashi Yuji, Ikeda Hiroaki, Nishimura Takashi
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, N-15, W-7, Sapporo 060-0815, Japan.
Immunol Lett. 2004 Aug 15;95(1):5-11. doi: 10.1016/j.imlet.2004.04.012.
Administration of NKT cell ligands, alpha-galactosylceramide (alpha-GalCer) resulted in the activation of both cytokine production and natural killing. These responses were abolished in both CD1d-deficient mice and Valpha14NKT-deficient mice. Therefore, NKT cells have been considered to be responsible cells for both cytokine production and natural killing. Here, we reevaluated a critical role of NKT and NK cells at early time after alpha-GalCer administration. Intracellular staining experiments demonstrated that NKT cells were the earliest source of both IL-4 and IFN-gamma production after alpha-GalCer administration in vivo. However, these alpha-GalCer-activated NKT cells exhibited no significant natural killing activity. In contrast, isolated NK1.1+CD3- classical NK cells exhibited greatly enhanced natural killing activity 6 h after alpha-GalCer administration. NKT cells, however, exhibited a strong cytotoxicity when they were activated and expanded with alpha-GalCer plus IL-2 in vitro. These results indicated that NKT cells act as regulatory cells via production of cytokines for activation of NK cell-mediated cytotoxicity in vivo at early phase after alpha-GalCer administration. Thus, NK cells rather than NKT cells may be a crucial early activated killer induced by alpha-GalCer in vivo.
给予NKT细胞配体α-半乳糖神经酰胺（α-GalCer）可导致细胞因子产生和自然杀伤的激活。在CD1d缺陷小鼠和Vα14 NKT缺陷小鼠中，这些反应均被消除。因此，NKT细胞被认为是细胞因子产生和自然杀伤的责任细胞。在此，我们重新评估了α-GalCer给药后早期NKT细胞和NK细胞的关键作用。细胞内染色实验表明，在体内给予α-GalCer后，NKT细胞是IL-4和IFN-γ产生的最早来源。然而，这些α-GalCer激活的NKT细胞未表现出明显的自然杀伤活性。相反，分离的NK1.1 + CD3-经典NK细胞在给予α-GalCer 6小时后表现出大大增强的自然杀伤活性。然而，当NKT细胞在体外被α-GalCer加IL-2激活和扩增时，它们表现出很强的细胞毒性。这些结果表明，在给予α-GalCer后的早期阶段，NKT细胞通过产生细胞因子作为调节细胞，以激活体内NK细胞介导的细胞毒性。因此，在体内，NK细胞而非NKT细胞可能是由α-GalCer诱导的关键早期激活杀手。
