Infectious Diseases Medicine Division, Vaccine and Immunotherapy Center, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America.
PLoS One. 2011 Apr 5;6(4):e18465. doi: 10.1371/journal.pone.0018465.
HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune dysregulatory functions that may limit anti-HIV antigen-specific T cell responses. We hypothesized that in the context of early SHIV infection, immune dysregulation of antigen-specific T-effector cell and regulatory functions would be detectable and that these would be associated or correlated with measurable concentrations of HIV-1gp120 in lymphoid tissues.
Rhesus macaques were intravaginally inoculated with a Clade C CCR5-tropic simian-human immunodeficiency virus, SHIV-1157ipd3N4. HIV-1gp120 levels, antigen-specificity, levels of apoptosis/anergy and frequency and function of Tregs were examined in lymph node and blood derived T cells at 5 and 12 weeks post inoculation.
RESULTS/CONCLUSIONS: We observed reduced responses to Gag in CD4 and gp120 in CD8 lymph node-derived T cells compared to the peripheral blood at 5 weeks post-inoculation. Reduced antigen-specific responses were associated with higher levels of PD-1 on lymph node-derived CD4 T cells as compared to peripheral blood and uninfected lymph node-derived CD4 T cells. Lymph nodes contained increased numbers of Tregs as compared to peripheral blood, which positively correlated with gp120 levels; T regulatory cell depletion restored CD8 T cell responses to Gag but not to gp120. HIV gp120 was also able to induce T regulatory cell chemotaxis in a dose-dependent, CCR5-mediated manner. These studies contribute to our broader understanding of the ways in which HIV-1 dysregulates T cell function and localization during early infection.
HIV-1 是一种病原体，T 细胞反应未能控制它。HIV-1gp120 是表面病毒包膜糖蛋白，与 CD4 T 细胞相互作用并介导进入。HIV-1gp120 被牵连到免疫失调功能，这可能限制抗 HIV 抗原特异性 T 细胞反应。我们假设，在早期 SHIV 感染的情况下，抗原特异性 T 效应细胞和调节功能的免疫失调将是可检测的，并且这些功能将与淋巴组织中可测量的 HIV-1gp120 浓度相关或相关联。
恒河猴通过阴道接种 CCR5 嗜性的人猴免疫缺陷病毒，SHIV-1157ipd3N4。在接种后 5 周和 12 周，在淋巴结和血液来源的 T 细胞中检查 HIV-1gp120 水平、抗原特异性、凋亡/无能水平以及 Treg 的频率和功能。
结果/结论：我们观察到，与外周血相比，在接种后 5 周时，淋巴结来源的 CD4 和 gp120 的 CD8 T 细胞对 Gag 的反应减少。与外周血和未感染的淋巴结来源的 CD4 T 细胞相比，淋巴节点来源的 CD4 T 细胞上 PD-1 的水平较高与较低的抗原特异性反应相关。与外周血相比，淋巴结含有更多的 Treg，与 gp120 水平呈正相关；Treg 细胞耗竭恢复了 CD8 T 细胞对 Gag 的反应，但对 gp120 没有反应。HIV gp120 还能够以剂量依赖的方式、通过 CCR5 介导诱导 Treg 细胞趋化。这些研究有助于我们更广泛地了解 HIV-1 在早期感染期间如何调节 T 细胞功能和定位。
