Plasmacytoid dendritic cells regulate Th cell responses through OX40 ligand and type IIFNs
Plasmacytoid dendritic cells regulate Th cell responses through OX40 ligand and type IIFNs
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DOI：
10.4049/jimmunol.172.7.4253
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Fukuhara, S
中科院分区：
文献类型：
--
作者：
Ito, T;Amakawa, R;Fukuhara, S
树突状细胞（Dendritic cells，DCs）在决定Th应答方面显示出功能可塑性，这取决于其成熟阶段或成熟信号传递给DCs。人浆细胞样树突状细胞（PDCs）在暴露于病毒或IL-3时可分别诱导Th1或Th2型免疫应答。在这项研究中，我们已经调查了Th极化能力的PDCs后，短期（24小时）或长期（72小时）的文化与刺激，并已评估的表达和功能的OX40配体（OX40L）在PDCs介导的Th极化除了I型IFN依赖性反应。IL-3处理的PDC表达OX40L，但响应于T细胞刺激（CD40配体或T细胞相互作用）几乎不产生IFN-α，导致通过OX40L依赖性机制优先引发Th2细胞。同时，PDC通过病毒感染（仙台病毒）迅速地被赋予高的潜能以发育产生IFN-γ的Th细胞，这取决于它们残余地产生IFN-α的能力。虽然仙台病毒刺激的PDCs在其成熟过程中同时表达OX40 L，但内源性I型IFN的Th1诱导作用可能克服并因此掩盖OX40 L依赖的Th2应答。然而，在成熟过程中响应仙台病毒在较长的72小时的时间内，OX40 L的表达水平上调，而残留的IFN-α产生能力下调，因此，延长仙台病毒刺激的PDCs诱导Th2反应在一定程度上。因此，PDCs具有独特的手段来决定对环境刺激的适当反应。
Dendritic cells (DCs) show a functional plasticity in determining Th responses depending on their maturational stage or on maturational signals delivered to the DCs. Human plasmacytoid DCs (PDCs) can induce either Th1- or Th2-type immune responses upon exposure to viruses or IL-3, respectively. In this study we have investigated the Th-polarizing capacity of PDCs after short (24-h) or long (72-h) culture with stimuli and have assessed the expression and function of OX40 ligand (OX40L) in PDC-mediated Th polarization in addition to type I IFN-dependent responses. IL-3-treated PDCs expressed OX40L, but produced almost no IFN-alpha in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. Meanwhile, PDCs were rapidly endowed by viral infection (Sendai virus) with a high potency to develop IFN-gamma-producing Th cells depending on their capacity to residually produce IFN-a. Although Sendai virus-stimulated PDCs simultaneously expressed OX40L in their maturational process, the Thl-inducing effect of endogenous type I IFNs may overcome and thus conceal the OX40L-dependent Th2 responses. However, during maturation in response to Sendai virus over the longer 72-h period, the expression level of OX40L was up-regulated, whereas the residual IFN-alpha-producing ability was down-regulated, and consequently, the PDCs with prolonged Sendai virus stimulation induced Th2 responses to some extent. Thus, PDCs have the distinct means to dictate an appropriate response to environmental stimuli.