Differential susceptibility of naïve, central memory and effector memory T cells to dendritic cell-mediated HIV-1 transmission.
Differential susceptibility of naïve, central memory and effector memory T cells to dendritic cell-mediated HIV-1 transmission.
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DOI：
10.1186/1742-4690-3-52
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发表时间：
2006-08-17
期刊：
影响因子：
3.3
通讯作者：
de Jong EC
中科院分区：
文献类型：
--
作者：
Groot F;van Capel TM;Schuitemaker J;Berkhout B;de Jong EC
树突状细胞（DC）已被提议通过在粘膜中捕获病毒并随后传递到CD 4 + T细胞来促进HIV-1的性传播。在人类中可以识别出几种T细胞亚群：启动对新抗原的免疫应答的幼稚T细胞（TN），以及对先前遇到的病原体做出反应的记忆T细胞。记忆T细胞库包括中央记忆细胞（TCM）和效应记忆细胞（TEM），其特征在于不同的归巢和效应功能。TEM细胞亚群可进一步分为效应Th 1和Th 2细胞，已被证明是HIV-1感染后病毒复制的主要靶细胞，并大量存在于粘膜组织中。我们测定了TN、TCM和TEM细胞对DC介导的HIV-1传播的易感性，发现各自T细胞亚群上的共受体表达是传播的决定性因素。因此，使用CCR 5的（R5）HIV-1最有效地传播到TEM细胞，使用CXCR 4的（X4）HIV-1优先传播到TN细胞。R5向TEM细胞的高效转移表明粘膜T细胞是DC介导的传播的重要靶点。这可能有助于在这些细胞中观察到的病毒复制的初始爆发。TN细胞是我们研究中DC介导的X4病毒传播的主要靶标，被认为不能有效地支持HIV-1复制。因此，我们的研究结果表明，DC可能在TN细胞对X4嗜性HIV-1的易感性中起决定性作用。
Dendritic cells (DC) have been proposed to facilitate sexual transmission of HIV-1 by capture of the virus in the mucosa and subsequent transmission to CD4+ T cells. Several T cell subsets can be identified in humans: naïve T cells (TN) that initiate an immune response to new antigens, and memory T cells that respond to previously encountered pathogens. The memory T cell pool comprises central memory (TCM) and effector memory cells (TEM), which are characterized by distinct homing and effector functions. The TEM cell subset, which can be further divided into effector Th1 and Th2 cells, has been shown to be the prime target for viral replication after HIV-1 infection, and is abundantly present in mucosal tissues. We determined the susceptibility of TN, TCM and TEM cells to DC-mediated HIV-1 transmission and found that co-receptor expression on the respective T cell subsets is a decisive factor for transmission. Accordingly, CCR5-using (R5) HIV-1 was most efficiently transmitted to TEM cells, and CXCR4-using (X4) HIV-1 was preferentially transmitted to TN cells. The highly efficient R5 transfer to TEM cells suggests that mucosal T cells are an important target for DC-mediated transmission. This may contribute to the initial burst of virus replication that is observed in these cells. TN cells, which are the prime target for DC-mediated X4 virus transmission in our study, are considered to inefficiently support HIV-1 replication. Our results thus indicate that DC may play a decisive role in the susceptibility of TN cells to X4 tropic HIV-1.
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