Kamijuku H, Nagata Y, Jiang X, Ichinohe T, Tashiro T, Mori K, Taniguchi M, Hase K, Ohno H, Shimaoka T, Yonehara S, Odagiri T, Tashiro M, Sata T, Hasegawa H, Seino K-i
Division of Bioregulation Research, Institute of Medical Science, St Marianna University School of Medicine, Miyamae-ku, Kawasaki City, Kanagawa, Japan.
Mucosal Immunol. 2008 May;1(3):208-18. doi: 10.1038/mi.2008.2. Epub 2008 Mar 5.
In a nasal vaccine against influenza, the activation of natural killer T (NKT) cells by intranasal coadministration of alpha-galactosylceramide (alpha-GalCer) can potently enhance protective immune responses. The results of this study show that the NKT cell-activated nasal vaccine can induce an effective cross-protection against different strains of influenza virus, including H5 type. To analyze the mechanism of NKT cell activation by this nasal vaccine, we prepared fluorescence-labeled alpha-GalCer by which we detect a direct interaction between NKT cells and alpha-GalCer-stored dendritic cells in nasal mucosa-associated tissues. Accordingly, although very few NKT cells exist at mucosa, the nasal vaccination induced a localized increase in NKT cell population, which is partly dependent on CXCL16/CXCR6. Furthermore, we found that NKT cell activation stimulates mucosal IgA production by a mechanism that is dependent on interleukin (IL)-4 production. These results strengthen the basis of nasal vaccination via NKT cell activation, which can induce immune cross-protection.
在一种抗流感的鼻内疫苗中，通过鼻内共同给予α-半乳糖神经酰胺（α-GalCer）激活自然杀伤T（NKT）细胞可有效增强保护性免疫反应。本研究结果表明，NKT细胞激活的鼻内疫苗可诱导针对不同株流感病毒（包括H5型）的有效交叉保护。为分析这种鼻内疫苗激活NKT细胞的机制，我们制备了荧光标记的α-GalCer，借此检测鼻黏膜相关组织中NKT细胞与储存α-GalCer的树突状细胞之间的直接相互作用。因此，尽管黏膜处存在的NKT细胞极少，但鼻内接种疫苗诱导了NKT细胞群体的局部增加，这部分依赖于CXCL16/CXCR6。此外，我们发现NKT细胞激活通过一种依赖于白细胞介素（IL）-4产生的机制刺激黏膜IgA的产生。这些结果强化了通过NKT细胞激活进行鼻内接种疫苗的基础，这种方法可诱导免疫交叉保护。
