Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines

Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines
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DOI:
10.1089/aid.2009.0290
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发表时间:
2010-10-01
影响因子:
1.5
通讯作者:
Rosenberg, Eric
Rosenberg, Eric
中科院分区:
医学4区
文献类型:
--
作者:
Rychert, Jenna;Strick, Daryld;Rosenberg, Eric

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急性HIV感染期间发生的事件可能导致HIV感染者常见的免疫功能障碍。在这一早期阶段,有高水平的病毒复制,CD4(+) T细胞数量和功能的丧失,促炎和免疫调节细胞因子的上调。造成这种情况的机制尚未完全了解。我们假设HIV包膜糖蛋白gp120参与了早期HIV感染期间的免疫功能障碍。在急性和早期HIV感染期间招募了一组受试者,我们测定了基线和6个月时血浆中gp120、tnf - α、IL-6、IL-10、ifn - α和ifn - γ的含量。在匹配的时间点,我们还测量了CD4(+) T细胞增殖、T细胞活化和凋亡。从109名受试者的血浆中筛选gp120。36例(33%)检测到gp120 (0.5 ~ 15.6 ng/ml)。gp120基线水平大于1 ng/ml的受试者在所有测试时间点的水平相似,即使在治疗后无法检测到病毒复制时也是如此。检测到gp120的受试者血浆IL-6、IL-10和tnf - α水平较高。与没有gp120的受试者相比,gp120患者的T细胞活化、增殖或凋亡水平没有差异。我们得出结论,gp120的持续表达发生在一小部分个体中。此外,gp120的存在与血浆IL-6、IL-10和tnf - α水平升高有关,这可能有助于早期HIV感染期间的免疫功能障碍。
Events that occur during acute HIV infection likely contribute to the immune dysfunction common in HIV-infected individuals. During this early stage, there is high-level viral replication, loss in CD4(+) T cell number and function, and an up-regulation of proinflammatory and immunoregulatory cytokines. The mechanisms responsible for this are not completely understood. We hypothesize that the HIV envelope glycoprotein, gp120, contributes to immune dysfunction during early HIV infection. Using a cohort of subjects enrolled during acute and early HIV infection, we determined the amount of gp120, TNF-alpha, IL-6, IL-10, IFN-alpha, and IFN-gamma in plasma at baseline and 6 months. At matched time points, we also measured CD4(+) T cell proliferation, T cell activation, and apoptosis. Plasma from 109 subjects was screened for gp120. Thirty-six subjects (33%) had detectable gp120 (0.5-15.6 ng/ml). Subjects with greater than 1 ng/ml of gp120 at baseline had similar levels at all time points tested, even when viral replication was undetectable due to therapy. Subjects with detectable gp120 had higher levels of plasma IL-6, IL-10, and TNF-alpha. There was no difference in the level of T cell activation, proliferation, or apoptosis in subjects with gp120 compared to those without. We conclude that persistent expression of gp120 occurs in a subset of individuals. Furthermore, the presence of gp120 is associated with higher levels of plasma IL-6, IL-10, and TNF-alpha, which may contribute to immune dysfunction during early HIV infection.