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纯化的抗HIV-1 IgG可有效抑制人未成熟单核细胞衍生树突状细胞中的HIV-1复制,且不会诱导其成熟。

Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti-HIV-1 IgG without induction of maturation.

作者信息

Holl Vincent, Peressin Maryse, Schmidt Sylvie, Decoville Thomas, Zolla-Pazner Susan, Aubertin Anne-Marie, Moog Christiane

机构信息

Institut de Virologie, 3 rue Koeberlé, F-67000 Strasbourg, France.

出版信息

Blood. 2006 Jun 1;107(11):4466-74. doi: 10.1182/blood-2005-08-3490. Epub 2006 Feb 9.

DOI:10.1182/blood-2005-08-3490
PMID:16469871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1895798/
Abstract

During mucosal HIV transmission, immature dendritic cells (DCs) present in the mucosa are among the first cellular targets of the virus. Previous studies have analyzed the inhibition of HIV-1 transfer from human mature DCs to T lymphocytes by neutralizing IgG, but so far no in vitro data regarding the capacity of antibodies to inhibit HIV-1 infection of immature DCs have been reported. Here, we found an increased HIV-inhibitory activity of monoclonal IgG and purified polyclonal IgG when immature monocyte-derived dendritic cells (iMDDCs) were used as target cells instead of autologous blood lymphocytes. We showed that FcgammaRII is involved in the mechanism for inhibiting HIV-1 infection of iMDDCs by IgG, whereas no induction of maturation was detected at concentrations of IgG that result in a 90% reduction of HIV replication. After induction of FcgammaRI expression on iMDDCs by IFN-gamma, an augmentation of the HIV-inhibitory activity of IgG, related to the expression of FcgammaRI, was observed. Taken together, our results demonstrate the participation of FcgammaRs in HIV-1 inhibition by IgG when iMDDCs are the targets. We propose that IgG is able to efficiently inhibit HIV-1 replication in iMDDCs and should be one of the components to be induced by vaccination.

摘要

在黏膜HIV传播过程中,黏膜中存在的未成熟树突状细胞(DCs)是该病毒最初的细胞靶标之一。先前的研究分析了通过中和性IgG抑制HIV-1从人成熟DCs转移至T淋巴细胞的情况,但迄今为止,尚无关于抗体抑制未成熟DCs感染HIV-1能力的体外数据报道。在此,我们发现当使用未成熟单核细胞来源的树突状细胞(iMDDCs)而非自体血淋巴细胞作为靶细胞时,单克隆IgG和纯化的多克隆IgG的HIV抑制活性增强。我们表明,FcγRII参与了IgG抑制iMDDCs感染HIV-1的机制,而在导致HIV复制减少90%的IgG浓度下未检测到成熟诱导。在用IFN-γ诱导iMDDCs表达FcγRI后,观察到与FcγRI表达相关的IgG的HIV抑制活性增强。综上所述,我们的结果证明当iMDDCs作为靶标时,FcγRs参与了IgG对HIV-1的抑制作用。我们提出,IgG能够有效抑制iMDDCs中的HIV-1复制,并且应该是疫苗接种诱导产生的成分之一。

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HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse.HIV-1转运至树突状细胞- T细胞感染性突触利用了一种四跨膜蛋白分选至免疫突触的途径。
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Covert human immunodeficiency virus replication in dendritic cells and in DC-SIGN-expressing cells promotes long-term transmission to lymphocytes.树突状细胞及表达DC-SIGN的细胞中人类免疫缺陷病毒的潜伏复制促进了其向淋巴细胞的长期传播。
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HIV-1 and the hijacking of dendritic cells: a tug of war.人类免疫缺陷病毒1型与树突状细胞的劫持:一场拔河比赛。
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