Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction
Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction
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DOI：
10.4049/jimmunol.175.7.4265
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Steinman, RM
中科院分区：
文献类型：
--
作者：
Granelli-Piperno, A;Pritsker, A;Steinman, RM
C型凝集素树突状细胞特异性JCAM 3-抓取非整合素（DC-SIGN）/CD 209有效结合几种病原体，包括HIV-1。DC-SIGN在培养的单核细胞来源的DC上表达，重要的是，它能够将HIV-1隔离在细胞内，并促进病毒向CD 4（+）T细胞的传播。为了研究DC-SIGN功能，我们产生了新的mAb。我们在这项研究中报告，这些和以前的抗DC-SIGN单克隆抗体主要标记非炎症人类淋巴结髓窦中的巨噬细胞。相反，除了偶尔的细胞外，在T细胞区域的大多数DC上未检测到表达。我们还注意到，单独的IL-4可以诱导CD 14（+）单核细胞和循环血DO中DC-SIGN的表达。然而，用Abs和DC-SIGN小干扰RNA阻断DC-SIGN并没有导致这些DO将HIV转移到T细胞的能力大幅降低，证实了显著的DC-SIGN非依赖性机制。阻断方法确实使DC-SIGN转染细胞的HIV-1传播减少了> 90%。DC-SIGN阻断也没有降低DC刺激MLR中T细胞增殖的能力。这些结果表明，DC-SIGN具有促进正常人淋巴结中巨噬细胞功能的潜力，并且DC不需要DC-SIGN来传播HIV或启动T细胞应答。
The C-type lectin dendritic cell-specific JCAM 3-grabbing nonintegrin (DC-SIGN)/CD209 efficiently binds several pathogens, including HIV-1. DC-SIGN is expressed on monocyte-derived DCs in culture, and importantly, it is able to sequester HIV-1 within cells and facilitate transmission of virus to CD4(+) T cells. To investigate DC-SIGN function, we have generated new mAbs. We report in this study that these and prior anti-DC-SIGN mAbs primarily label macrophages in the medullary sinuses of noninflamed human lymph node. In contrast, expression is not detected on most DCs in the T cell area, except for occasional cells. We also noted that IL-4 alone can induce expression of DC-SIGN in CD14(+) monocytes and circulating blood DO. However, blockade of DC-SIGN with Abs and DC-SIGN small interfering RNA did not result in a major reduction in the capacity of these DO to transfer HIV to T cells, confirming significant DC-SIGN-independent mechanisms. The blocking approaches did reduce HIV-1 transmission by DC-SIGN-transfected cells by > 90%. DC-SIGN blockade also did not reduce the ability of DCs to stimulate T cell proliferation in the MLR. These results indicate that DC-SIGN has the potential to contribute to macrophage function in normal human lymph node, and that DCs do not require DC-SIGN to transmit HIV or to initiate T cell responses.