Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs.

Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs.
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浆细胞样 DC 帮助淋巴结 DC 诱导抗 HSV CTL。

DOI:
10.1084/jem.20041961
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发表时间:
2005-08-01
影响因子:
15.3
通讯作者:
Matsushima, K
Matsushima, K
中科院分区:
医学1区
文献类型:
--
作者:
Yoneyama, H;Matsuno, K;Toda, E;Nishiwaki, T;Matsuo, N;Nakano, A;Narumi, S;Lu, B;Gerard, C;Ishikawa, S;Matsushima, K

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抗病毒细胞介导的免疫是由淋巴结(LN)中的树突状细胞(DC)网络启动的。已知浆细胞样DC(pDC)迁移至炎症淋巴结并产生干扰素(IFN)-α,但其在抗病毒T细胞免疫中的其他作用尚不清楚。我们报告说,LN招募的pDC被激活,以创建本地的免疫领域,产生抗病毒的细胞毒性T淋巴细胞(CTL)与LNDCs,在皮肤单纯疱疹病毒(HSV)感染的模型。虽然单独的pDC不能诱导CTL,但pDC的体内消耗损害CTL介导的病毒根除。来自pDC缺失小鼠的LNDC显示与T细胞的簇形成和抗原呈递至引发CTL受损。将来自野生型但非CXCR 3缺陷型小鼠的循环pDC前体转移至pDC耗尽的小鼠恢复了受损LNDC的CTL诱导。体外共培养实验表明,pDC提供帮助信号,以CD 2和CD 40 L依赖性方式恢复受损的LNDC。pDC衍生的IFN-α进一步刺激回收的LNDC诱导CTL。因此,pDC在初次免疫应答中为LNDC提供的帮助似乎是最佳诱导抗HSV CTL的关键。
Antiviral cell–mediated immunity is initiated by the dendritic cell (DC) network in lymph nodes (LNs). Plasmacytoid DCs (pDCs) are known to migrate to inflamed LNs and produce interferon (IFN)-α, but their other roles in antiviral T cell immunity are unclear. We report that LN-recruited pDCs are activated to create local immune fields that generate antiviral cytotoxic T lymphocytes (CTLs) in association with LNDCs, in a model of cutaneous herpes simplex virus (HSV) infection. Although pDCs alone failed to induce CTLs, in vivo depletion of pDCs impaired CTL-mediated virus eradication. LNDCs from pDC-depleted mice showed impaired cluster formation with T cells and antigen presentation to prime CTLs. Transferring circulating pDC precursors from wild-type, but not CXCR3-deficient, mice to pDC-depleted mice restored CTL induction by impaired LNDCs. In vitro co-culture experiments revealed that pDCs provided help signals that recovered impaired LNDCs in a CD2- and CD40L-dependent manner. pDC-derived IFN-α further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs.
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