Institut Pasteur, Unité Régulation des Infections Rétrovirales.
INSERM U976, Laboratory of Human Immunology, Pathophysiology and Immunotherapy, Hôpital Saint-Louis, Université Paris Diderot.
AIDS. 2019 Jul 1;33(8):1283-1292. doi: 10.1097/QAD.0000000000002196.
HIV controllers (HICs) are rare HIV-infected individuals able to maintain undetectable viremia in the absence of antiretroviral treatment. Although HIV-specific cytotoxic T cells have been well deciphered in HIC, γδ T lymphocytes remain largely uncharacterized. The aim of this study was to analyse phenotypic and functional characteristics of γδ T cells and their relationship with immune activation, which remains abnormally elevated and associated with comorbidities in HICs.
Peripheral blood mononuclear cells (PBMCs) were isolated from 16 HICs, 16 patients with untreated chronic HIV infection (UT-CHI) and 20 healthy donors. Surface marker expression and cytokine production by γδ T cells were analysed by flow cytometry.
Despite normal frequencies of total γδ T cells, the Vδ2/Vδ2 ratio was significantly reduced in HIC, albeit to a lesser extent than UT-CHI patients. Of note, nine HICs showed elevated Vδ2 γδ T cells, as patients with UT-CHI, which was associated with higher CD8 T-cell activation. Interleukin (IL)-17-production by γδ T cells (Tγδ17) was better preserved in HIC than in UT-CHI patients. Proportion of total γδ T cells positively correlated with CD8 T-cell activation and HIV-DNA, IP-10 and sCD14 levels. Conversely, Tγδ17 cells negatively correlated with CD8 T-cell activation and plasma sCD14 levels. Moreover, transforming growth factor (TGF)-β producing Vδ2 T cells were as dramatically depleted in HIC as in UT-CHI patients.
The relative preservation of IL-17-producing γδ T cells in HIC and their negative association with immune activation raise the hypothesis that Tγδ17 cells - potentially through prevention of microbial translocation - may participate in the control of chronic systemic immune activation.
HIV 控制器（HIC）是一种罕见的 HIV 感染者，在没有抗逆转录病毒治疗的情况下能够维持无法检测到的病毒血症。尽管在 HIC 中已经很好地阐明了 HIV 特异性细胞毒性 T 细胞，但 γδ T 淋巴细胞仍然在很大程度上未被描述。本研究旨在分析 γδ T 细胞的表型和功能特征及其与免疫激活的关系，免疫激活在 HIC 中仍然异常升高，并与合并症相关。
从 16 名 HIC、16 名未经治疗的慢性 HIV 感染（UT-CHI）患者和 20 名健康供体中分离外周血单核细胞（PBMC）。通过流式细胞术分析 γδ T 细胞的表面标志物表达和细胞因子产生。
尽管总 γδ T 细胞的频率正常，但 HIC 中的 Vδ2/Vδ2 比值显著降低，尽管程度不及 UT-CHI 患者。值得注意的是，9 名 HIC 患者的 Vδ2 γδ T 细胞升高，与 UT-CHI 患者相同，这与 CD8 T 细胞激活增加有关。与 UT-CHI 患者相比，HIC 中 γδ T 细胞（Tγδ17）产生的白细胞介素（IL）-17 保存更好。总 γδ T 细胞的比例与 CD8 T 细胞激活和 HIV-DNA、IP-10 和 sCD14 水平呈正相关。相反，Tγδ17 细胞与 CD8 T 细胞激活和血浆 sCD14 水平呈负相关。此外，HIC 中 TGF-β 产生的 Vδ2 T 细胞与 UT-CHI 患者一样明显耗竭。
HIC 中 IL-17 产生的 γδ T 细胞的相对保存及其与免疫激活的负相关提出了这样的假设，即 Tγδ17 细胞 - 可能通过防止微生物易位 - 可能参与慢性全身性免疫激活的控制。
