Dendritic cell-mediated HIV-1 transmission to T cells of LAD-1 patients is impaired due to the defect in LFA-1.
Dendritic cell-mediated HIV-1 transmission to T cells of LAD-1 patients is impaired due to the defect in LFA-1.
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由于LFA-1缺陷，树突状细胞介导的HIV-1向LAD-1患者的T细胞传播受损。
DOI：
10.1186/1742-4690-3-75
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发表时间：
2006-11-01
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;Kuijpers TW;Berkhout B;de Jong EC
树突状细胞（DC）已被提出介导性HIV-1传播，通过捕获粘膜中的病毒并随后将其呈递给CD 4 + T细胞。我们以前已经证明，表达更高水平的细胞间粘附分子-1（ICAM-1）的DC亚群是更好的HIV-1递质。ICAM-1结合T细胞上的白细胞功能相关分子-1（LFA-1），LFA-1是一种负责免疫突触处粘附和信号传导的整合素。为了证实ICAM-1- LFA-1相互作用的重要性，我们对来自白细胞粘附缺陷1型（LAD-1）患者的LFA-1阴性白细胞进行了传递实验。我们清楚地表明，与健康对照组相比，DC介导的HIV-1向LAD-1 T细胞的传播受损。此外，HIV-1从一个独特的LAD-1患者的T细胞传播到一个充分表征的LFA-1激活缺陷也受到损害，这表明LFA-1的激活是有效传播的关键。DC和LAD-1 T细胞之间的细胞粘附性降低也可以通过HIV-1传播后显著较小的DC-T细胞簇来说明。通过利用来自独特患者的LFA-1缺陷细胞，这项研究为DC传播HIV-1的机制提供了更多的见解。这可能为减少HIV-1的性传播提供新的治疗选择。
Dendritic cells (DC) have been proposed to mediate sexual HIV-1 transmission by capturing the virus in the mucosa and subsequently presenting it to CD4+ T cells. We have demonstrated before that DC subsets expressing higher levels of intercellular adhesion molecule-1 (ICAM-1) are better HIV-1 transmitters. ICAM-1 binds leukocyte function-associated molecule-1 (LFA-1) on T cells, an integrin responsible for adhesion and signaling at the immunological synapse. To corroborate the importance of the ICAM-1— LFA-1 interaction, we performed transmission experiments to LFA-1 negative leukocytes from Leukocyte Adhesion Deficiency type 1 (LAD-1) patients. We clearly show that DC-mediated HIV-1 transmission to LAD-1 T cells is impaired in comparison to healthy controls. Furthermore, HIV-1 transmission to T cells from a unique LAD-1 patient with a well characterized LFA-1 activation defect was impaired as well, demonstrating that activation of LFA-1 is crucial for efficient transmission. Decreased cell adhesion between DC and LAD-1 T cells could also be illustrated by significantly smaller DC-T cell clusters after HIV-1 transmission. By making use of LFA-1 defect cells from unique patients, this study provides more insight into the mechanism of HIV-1 transmission by DC. This may offer new treatment options to reduce sexual transmission of HIV-1.
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