Native and genetically inactivated pertussis toxins induce human dendritic cell maturation and synergize with lipopolysaccharide in promoting T helper type 1 responses
Native and genetically inactivated pertussis toxins induce human dendritic cell maturation and synergize with lipopolysaccharide in promoting T helper type 1 responses
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DOI：
10.1086/341510
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发表时间：
2002-08-01
影响因子：
6.4
通讯作者：
Cassone, A
中科院分区：
文献类型：
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作者：
Ausiello, CM;Fedele, G;Cassone, A
研究了百日咳毒素（PT）诱导人单核细胞来源的树突状细胞（DC）成熟和功能活动的能力。天然PT（nPT）和遗传脱毒PT（dPT）均有效促进DC上CD 80、CD 86、人白细胞抗原-DR和CD 83标记物的表达、同种异体反应性抗原呈递和细胞因子（主要是干扰素（IFN）-γ）的产生。虽然它们不影响由脂多糖（LPS）刺激的DC产生白细胞介素（IL）-10，但是nPT和dPT都与LPS强烈协同产生IL-12。PT + LPS刺激的DC分泌可溶性因子，促进初始T细胞产生IFN-γ，但不产生IL-4和IL-5。辅助性T细胞1型（Th 1）极化，作为同种异体反应性抗原提呈，被抗IL-12单克隆抗体抑制。这些发现支持了nPT除了诱导特异性免疫应答之外，还是一种有效的Th 1佐剂，并且dPT完全保留了这种佐剂性的观点。PT和LPS在IL-12产生中的协同作用可能与疫苗诱导的保护机制有关。
The capacity of pertussis toxin (PT) to induce maturation and functional activities of human monocyte-derived dendritic cells (DCs) was investigated. Both native PT (nPT) and genetically detoxified PT (dPT) efficiently promoted expression on DCs of CD80, CD86, human leukocyte antigen-DR, and CD83 markers, alloreactive antigen presentation, and cytokine production, primarily interferon (IFN)-gamma. Although they did not affect interleukin (IL)-10 production by lipopolysaccharide (LPS)-stimulated DCs, both nPT and dPT strongly synergized with LPS for IL-12 production. PTs plus LPS-stimulated DCs secreted soluble factors fostering IFN-gamma but not IL-4 and IL-5 production by naive T cells. T helper type 1 (Th1) polarization was, as alloreactive antigen presentation, inhibited by anti-IL-12 monoclonal antibody. These findings support the notion that nPT, in addition to inducing specific immune response, is a potent Th1 adjuvant and that dPT fully preserves this adjuvanticity. The synergic interaction between PT and LPS in IL-12 production might be relevant for the mechanisms of vaccine-induced protection.