Smithgall M D, Wong J G, Critchett K E, Haffar O K
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
J Immunol. 1996 Mar 15;156(6):2324-30.
We have investigated the effect of exogenous IL-7 on replication of HIV-1 in PBMCs isolated from asymptomatic, chronically infected donors. We show that IL-7 induced virus replication and increased proviral DNA levels in CD8- PBMC cultures. IL-7 also increased the levels of doubly spliced HIV-1 tat RNA in these cultures. In comparison, IL-2 induced lower levels of virus production than IL-7, but had a more pronounced effect on cell proliferation. The IL-7-mediated increase in virus replication was not inhibited by neutralizing mAbs to IL-1 beta, IL-2, IL-6, or TNF-alpha, and was only partially dependent on ligation of the T cell accessory molecule CD28. CD8+ cells inhibited the increase in viral replication following IL-7 stimulation, but did not prevent virus replication following ligation of CD3 in the presence of IL-7. The data shows that IL-7 regulates HIV-1 replication in naturally infected PBMCs.
我们研究了外源性白细胞介素-7(IL-7)对从无症状慢性感染供体分离的外周血单核细胞(PBMCs)中HIV-1复制的影响。我们发现,IL-7可诱导病毒复制,并增加CD8阴性PBMC培养物中前病毒DNA水平。IL-7还可增加这些培养物中双剪接HIV-1反式激活因子(tat)RNA的水平。相比之下,IL-2诱导的病毒产生水平低于IL-7,但对细胞增殖的影响更为显著。IL-7介导的病毒复制增加不受针对IL-1β、IL-2、IL-6或肿瘤坏死因子-α(TNF-α)的中和单克隆抗体的抑制,且仅部分依赖于T细胞辅助分子CD28的连接。CD8阳性细胞可抑制IL-7刺激后病毒复制的增加,但在IL-7存在的情况下,CD3连接后并不能阻止病毒复制。数据表明,IL-7可调节自然感染PBMCs中HIV-1的复制。