Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells.
Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells.
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DOI：
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发表时间：
2001
影响因子：
5.4
通讯作者：
A. Krug;S. Rothenfusser;V. Hornung;B. Jahrsdörfer;S. Blackwell;Z. Ballas;S. Endres;A. Krieg;G. Hartmann
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文献类型：
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作者：
A. Krug;S. Rothenfusser;V. Hornung;B. Jahrsdörfer;S. Blackwell;Z. Ballas;S. Endres;A. Krieg;G. Hartmann
未成熟的浆细胞样树突状细胞（PDC）与病毒感染后的主要I型IFN产生细胞相同。含有未甲基化CpG基序的寡聚脱氧核苷酸（CpG ODN）可被脊椎动物免疫系统识别。以前，我们描述了强激活人B细胞和人血液树突状细胞的CpG ODN。在这里，我们描述了不同的含CpG的寡核苷酸序列，与以前描述的CpG ODN，诱导大量的IFN-α和IFN-β在外周血单核细胞（PBMC）。IFN-α的细胞内染色显示，在PBMC内，CpG ODN诱导的IFN-α仅由PDC产生。与IFN-α不同，TNF-α在PDC中被所有测试的CpG ODN上调。纯化的PDC对CpG ODN有反应，表明CpG ODN直接激活PDC。最具活性的序列诱导每个单个PDC产生高达5 pg的IFN-α，导致富集PDC的PBMC上清液中超过400 ng/ml的IFN-α。CpG ODN刺激IFN-α的效力与其刺激NK细胞裂解活性的能力相关，而纯化的NK细胞对CpG ODN无应答。PBMC中IFN γ的产生依赖于CpG ODN诱导的IFN-α/β，如IFN-α/β阻断抗体所证明的。IFN-α诱导的CpG ODN强烈支持TCR触发的CD 4 T细胞的IFN-γ产生，但在刺激B细胞方面不如其他CpG ODN活性。总之，我们的结果表明，特定的CpG ODN序列存在，由于高IFN-α/β诱导PDC，诱导一组典型的病毒感染的免疫应答。
The immature plasmacytoid dendritic cell (PDC) is identical with the principal type I IFN-producing cell upon viral infection. Oligodeoxynucleotides which contain unmethylated CpG motifs (CpG ODN) are recognized by the vertebrate immune system. Previously, we described CpG ODN that strongly activate human B cells and human blood dendritic cells. Here we describe distinct CpG-containing oligonucleotide sequences which, in contrast to previously described CpG ODN, induced high amounts of IFN-alpha and IFN-beta in peripheral blood mononuclear cells (PBMC). Intracellular staining for IFN-alpha revealed that within PBMC CpG ODN-induced IFN-alpha is produced exclusively by PDC. Unlike IFN-alpha, TNF-alpha is up-regulated in PDC by all CpG ODN tested. Purified PDC responded to CpG ODN, demonstrating direct activation of PDC by CpG ODN. The most active sequence induced the production of up to 5 pg IFN-alpha per single PDC, resulting in more than 400 ng/ml IFN-alpha in the supernatant of PBMC enriched for PDC. The potency of CpG ODN to stimulate IFN-alpha correlated with their ability to stimulate NK cell lytic activity, while purified NK cells did not respond to CpG ODN. IFNgamma production in PBMC was dependent on CpG ODN-induced IFN-alpha/beta as demonstrated by IFN-alpha/beta blocking antibodies. IFN-alpha-inducing CpG ODN strongly supported IFN-gamma production of TCR-triggered CD4 T cells but were less active than other CpG ODN in stimulating B cells. In conclusion our results demonstrate that particular CpG ODN sequences exist which, due to high IFN-alpha/beta induction in PDC, induce a set of immune responses typical for viral infection.