Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs
Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs
复制标题
DOI：
10.1038/ni.1848
复制
发表时间：
2010-04-01
影响因子：
30.5
通讯作者：
Kurts, Christian
中科院分区：
文献类型：
--
作者：
Semmling, Verena;Lukacs-Kornek, Veronika;Kurts, Christian
交叉引发允许树突状细胞 (DC) 诱导细胞毒性 T 细胞 (CTL) 对细胞外抗原的反应。 DC 需要同源“许可”来进行交叉启动，通常是通过辅助 T 细胞进行。在这里，我们展示了自然杀伤 T (NKT) 细胞识别微生物或合成糖脂抗原的同源许可的替代机制。这种许可导致交叉启动 CD8(α)(+) DC 产生趋化因子 CCL17，从而吸引表达趋化因子受体 CCR4 的初始 CTL。相比之下，获得辅助 T 细胞许可的 DC 使用 CCR5 配体招募 CTL。因此，根据它们遇到的抗原类型，DC 可以被 NKT 细胞或辅助 T 细胞交叉引发，并使用至少两个独立的趋化因子途径来吸引初始 CTL。由于这些趋化因子具有协同作用，因此有可能被用来改善疫苗接种。
Cross-priming allows dendritic cells (DCs) to induce cytotoxic T cell (CTL) responses to extracellular antigens. DCs require cognate 'licensing' for cross-priming, classically by helper T cells. Here we demonstrate an alternative mechanism for cognate licensing by natural killer T (NKT) cells recognizing microbial or synthetic glycolipid antigens. Such licensing caused cross-priming CD8(alpha)(+) DCs to produce the chemokine CCL17, which attracted naive CTLs expressing the chemokine receptor CCR4. In contrast, DCs licensed by helper T cells recruited CTLs using CCR5 ligands. Thus, depending on the type of antigen they encounter, DCs can be licensed for cross-priming by NKT cells or helper T cells and use at least two independent chemokine pathways to attract naive CTLs. Because these chemokines acted synergistically, this can potentially be exploited to improve vaccinations.