Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines.
Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines.
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使用细胞因子的组合在潜在感染的CD4+ T细胞中诱导HIV-1复制。
DOI：
10.1084/jem.188.1.83
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发表时间：
1998-07-06
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尽管已经证明某些细胞因子，特别是促炎细胞因子，可以增强HIV-1感染个体的外周血单核细胞（PBMC）中正在进行的病毒复制，但尚不清楚这些细胞因子在潜伏感染的静息CD 4 + T细胞中诱导HIV-1复制中起什么作用。本研究表明，促炎细胞因子白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α与免疫调节细胞因子IL-2的体外组合是来自未接受过抗逆转录病毒治疗以及正在接受高效抗逆转录病毒治疗（HAART）的HIV感染个体的高度纯化、潜伏感染、静息CD 4 + T细胞中病毒复制的强效诱导剂。在体外存在HAART的情况下，这种细胞因子组合诱导的病毒复制被完全抑制。考虑到一系列细胞因子，包括IL-6、TNF-α和IL-2，在淋巴组织的微环境中大量表达，而淋巴组织是潜伏的病毒库，这种细胞因子组合对HIV的诱导可能部分解释了在HAART中断的HIV感染个体中经常观察到的可检测的血浆病毒血症的重现。此外，由于很可能这些感染的细胞在病毒激活后死亡，并且HAART防止病毒扩散到相邻细胞，因此观察到这种细胞因子的组合可以显著诱导该储库中的病毒复制，这可能对接受HAART的患者中HIV潜伏储库的激活介导的减少具有重要意义。
Although it has been demonstrated that certain cytokines, particularly proinflammatory cytokines, can enhance ongoing viral replication in peripheral blood mononuclear cells (PBMCs) of HIV-1–infected individuals, it is unclear what role these cytokines play in the induction of HIV-1 replication in latently infected, resting CD4+ T cells. This study demonstrates that the in vitro combination of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α together with the immunoregulatory cytokine IL-2 are potent inducers of viral replication in highly purified, latently infected, resting CD4+ T cells derived from HIV-infected individuals who are antiretroviral therapy–naive as well as those who are receiving highly active antiretroviral therapy (HAART). Viral replication induced by this combination of cytokines was completely suppressed in the presence of HAART in vitro. Given that an array of cytokines, including IL-6, TNF-α, and IL-2, are copiously expressed in the microenvironment of the lymphoid tissues, which harbor the latent viral reservoirs, induction of HIV by this combination of cytokines may in part explain the commonly observed reappearance of detectable plasma viremia in HIV-infected individuals in whom HAART was discontinued. Moreover, since it is likely that these infected cells die upon activation of virus and that HAART prevents spread of virus to adjacent cells, the observation that this combination of cytokines can markedly induce viral replication in this reservoir may have important implications for the activation-mediated diminution of the latent reservoir of HIV in patients receiving HAART.