Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-Universität, Bonn, Germany.
Nat Immunol. 2010 Apr;11(4):313-20. doi: 10.1038/ni.1848. Epub 2010 Feb 28.
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 CD8alpha(+) 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.
交叉呈递使树突状细胞 (DC) 能够诱导细胞毒性 T 细胞 (CTL) 对细胞外抗原产生反应。DC 对交叉呈递的要求是同源“许可”，经典的是由辅助 T 细胞提供。在这里，我们通过自然杀伤 T (NKT) 细胞识别微生物或合成糖脂抗原来证明同源许可的另一种机制。这种许可导致交叉呈递 CD8alpha(+) DC 产生趋化因子 CCL17，吸引表达趋化因子受体 CCR4 的幼稚 CTL。相比之下，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 细胞许可进行交叉呈递，并使用至少两种独立的趋化因子途径来吸引幼稚 CTL。由于这些趋化因子具有协同作用，因此可以利用这一点来改进疫苗接种。
