Subset of DC-SIGN+ dendritic cells in human blood transmits HIV-1 to T lymphocytes
Subset of DC-SIGN+ dendritic cells in human blood transmits HIV-1 to T lymphocytes
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DOI：
10.1182/blood-2001-12-0179
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发表时间：
2002-09-01
期刊：
影响因子：
20.3
通讯作者：
van Kooyk, Y
中科院分区：
文献类型：
--
作者：
Engering, A;van Vliet, SJ;van Kooyk, Y
树突状细胞（DC）特异性分子DC-SIGN是HIV-1包膜糖蛋白gp 120的受体，对HIV-1的传播至关重要。DC-SIGN由DC表达，包括单核细胞来源的DC和几种组织（包括粘膜和淋巴结）中的DC。为了鉴定血液中可能参与HIV-1通过血液感染的DC-SIGN（+）DC，我们分析了DC-SIGN在人血细胞中的表达。在这里，我们描述了一个子集的DC在人血液中的特征，从T-/NK-/B-细胞耗尽的外周血单核细胞（PBMC）的基础上表达DC-SIGN的分离。该亚群共表达CD 14、CD 16和CD 33，因此是骨髓来源的。与CD 14（+）单核细胞相比，DC-SIGN（+）血细胞显示DC样形态，并表达抗原呈递细胞的标志物，包括CD 1c、CD 11b、CD 11 c、CD 86和高水平的主要组织相容性复合体（MHC）I类和11类分子。该DC群体不同于其他描述的CD 14（-）血液DC亚群。在功能上，DC-SIGN（+）血液DC能够刺激同种异体T细胞的增殖，并且在用脂多糖（LPS）活化后可以产生肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。当它们遇到HIV-1时，少量的这些血液DC-SIGN（+）DC增强了反式T淋巴细胞的感染，而血液单核细胞和CD 14（-）血液DC不能传播HIV-1。因此，DC-SIGN（+）血液DC可以是HIV-1通过血液传播的第一个靶点;它们可以通过DC-SIGN捕获微量的HIV-1，并将HIV-1转移到反式感染靶T细胞。
The dendritic cell (DC)-specific molecule DC-SIGN is a receptor for the HIV-1 envelope glycoprotein gp120 and is essential for the dissemination of HIV-1. DC-SIGN is expressed by DCs, both monocyte-derived DCs and DCs in several tissues, including mucosa and lymph nodes. To identify a DC-SIGN(+) DC in blood that may be involved in HIV-1 infection through blood, we have analyzed the expression of DC-SIGN in human blood cells. Here we describe the characterization of a subset of DCs in human blood, isolated from T-/NK-/B-cell-depleted peripheral blood mononuclear cells (PBMCs) on the basis of expression of DC-SIGN. This subset co-expresses CD14, CD16, and CD33 and is thus of myeloid origin. In contrast to CD14(+) monocytes, DC-SIGN(+) blood cells display a DC-like morphology and express markers of antigen-presenting cells, including CD1c, CD11b, CD11c, CD86, and high levels of major histocompatibility complex (MHC) class I and 11 molecules. This DC population differs from other described CD14(-) blood DC subsets. Functionally, DC-SIGN(+) blood DCs are able to stimulate proliferation of allogeneic T cells and can produce tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) upon activation with lipopolysaccharide (LPS). When they encounter HIV-1, low amounts of these blood DC-SIGN(+) DCs enhance infection of T lymphocytes In trans, whereas blood monocytes and CD14(-) blood DCs are not capable of transmitting HIV-1. Therefore DC-SIGN(+) blood DCs can be the first target for HIV-1 upon transmission via blood; they can capture minute amounts of HIV-1 through DC-SIGN and transfer HIV-1 to infect target T cells in trans.