Paget Christophe, Bialecki Emilie, Fontaine Josette, Vendeville Catherine, Mallevaey Thierry, Faveeuw Christelle, Trottein François
Institut National de Santé et de Recherche Médicale, Unité 547, Lille, France.
J Immunol. 2009 Feb 15;182(4):1846-53. doi: 10.4049/jimmunol.0802492.
Unmethylated CpG oligodeoxynucleotides (ODNs), by activating cells of the innate immune system, such as dendritic cells and NK cells, are potent adjuvants for type 1 immune responses. In the present study, we aimed to investigate the role of invariant NKT (iNKT) cells, a subset of lipid-reactive innate lymphocytes, in CpG ODN-induced innate and acquired type 1 responses. Our data show that, in response to the CpG ODN type B 1826, splenic and hepatic iNKT cells become activated and produce IFN-gamma, but not IL-4, both in vitro and in vivo. This Th1 bias is independent from the Ag-presenting molecule CD1d and strongly requires IL-12, at least in vitro. We also report that iNKT cell activation, in response to CpG ODN type B, results in the transactivation of NK cells. To address the potential role of iNKT cells in type 1 innate immunity induced by CpG ODN, a murine model of malignant melanoma was used. We show that CpG ODN type B protects mice against B16F10-induced lung metastasis in wild-type mice, but in a less efficient manner in iNKT cell-deficient animals. Finally, we report that immunization of wild-type mice with CpG ODN type B plus keyhole limpet hemocyanin biases the immune response toward a Th1 direction, an effect strongly mediated by iNKT cells. We conclude that iNKT cells amplify the innate and acquired response to CpG ODN type B, with potentially important consequences for the regulation of immune responses.
未甲基化的CpG寡脱氧核苷酸（ODN）通过激活天然免疫系统的细胞，如树突状细胞和自然杀伤细胞，成为1型免疫反应的有效佐剂。在本研究中，我们旨在探讨不变自然杀伤T细胞（iNKT细胞），一种脂质反应性天然淋巴细胞亚群，在CpG ODN诱导的天然和获得性1型反应中的作用。我们的数据表明，在对CpG ODN B型1826的反应中，脾脏和肝脏中的iNKT细胞在体外和体内均被激活并产生干扰素-γ，但不产生白细胞介素-4。这种Th1偏向独立于抗原呈递分子CD1d，并且至少在体外强烈需要白细胞介素-12。我们还报告说，对CpG ODN B型的反应中，iNKT细胞的激活导致自然杀伤细胞的反式激活。为了研究iNKT细胞在CpG ODN诱导的1型天然免疫中的潜在作用，使用了恶性黑色素瘤的小鼠模型。我们表明，CpG ODN B型在野生型小鼠中可保护其免受B16F10诱导的肺转移，但在iNKT细胞缺陷动物中效果较差。最后，我们报告说，用CpG ODN B型加钥孔戚血蓝蛋白免疫野生型小鼠会使免疫反应偏向Th1方向，这一效应强烈由iNKT细胞介导。我们得出结论，iNKT细胞放大了对CpG ODN B型的天然和获得性反应，对免疫反应的调节可能具有重要意义。
