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首页> 外文期刊>EBioMedicine >Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway
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Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway

机译：树突状细胞可有效清除潜在的HIV-1，而不受TCR刺激，从而激活PI3K-Akt-mTOR途径

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Background The latent HIV-1 reservoir in treated patients primarily consists of resting memory CD4sup+/sup T cells. Stimulating the T-cell receptor (TCR), which facilitates transition of resting into effector T cells, is the most effective strategy to purge these latently infected cells. Here we supply evidence that TCR-stimulated effector T cells still frequently harbor latent HIV-1. Methods Primary HIV-1 infected cells were used in a latency assay with or without dendritic cells (DCs) and reversion of HIV-1 latency was determined, in the presence or absence of specific pathway inhibitors. Findings Renewed TCR-stimulation or subsequent activation with latency reversing agents (LRAs) did not overcome latency. However, interaction of infected effector cells with DCs triggered further activation of latent HIV-1. When compared to TCR-stimulation only, CD4sup+/sup T cells from aviremic patients receiving TCR?+?DC-stimulation reversed latency more frequently. Such a “one-two punch” strategy seems ideal for purging the reservoir. We determined that DC contact activates the PI3K-Akt-mTOR pathway in CD4sup+/sup T cells. Interpretation This insight could facilitate the development of a novel class of potent LRAs that purge latent HIV beyond levels reached by T-cell activation.
机译：背景治疗患者的潜在HIV-1储库主要由静息记忆CD4 + T细胞组成。刺激T细胞受体（TCR）有助于清除静息细胞转化为效应T细胞，是清除这些潜伏感染细胞的最有效策略。在这里，我们提供证据表明，TCR刺激的效应T细胞仍然经常带有潜在的HIV-1。方法将原代HIV-1感染的细胞用于有或没有树突状细胞（DC）的潜伏期测定中，并在有或没有特定途径抑制剂的情况下测定HIV-1潜伏期的逆转。发现更新的TCR刺激或随后的潜伏期逆转剂（LRA）激活不能克服潜伏期。但是，感染的效应细胞与DC的相互作用触发了潜在HIV-1的进一步激活。当仅与TCR刺激相比时，接受TCRα+ΔDC刺激的非飞行症患者的CD4 + T细胞更经常地逆转潜伏期。这样的“一两次打”策略似乎是清除储层的理想选择。我们确定直流接触激活了CD4 + T细胞中的PI3K-Akt-mTOR途径。解释这种见解可以促进新型有效LRA的开发，这些LRA可以清除潜在的HIV，使其超过T细胞活化所达到的水平。

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