Vo Dang-Nghiem, Leventoux Nicolas, Campos-Mora Mauricio, Gimenez Sandrine, Corbeau Pierre, Villalba Martin
IRMB, University Montpellier, INSERM, 34295 Montpellier, France.
Institute for Human Genetics, CNRS-Montpellier University, UMR9002, 141 Rue de la Cardonille, CEDEX, 34396 Montpellier, France.
Vaccines (Basel). 2022 Apr 28;10(5):688. doi: 10.3390/vaccines10050688.
NK cells play a major role in the antiviral immune response, including against HIV-1. HIV-1 patients have impaired NK cell activity with a decrease in CD56 NK cells and an increase in the CD56CD16 subset, and recently it has been proposed that a population of CD56NKG2CKIRCD57 cells represents antiviral memory NK cells. Antiretroviral therapy (ART) partly restores the functional activity of this lymphocyte lineage. NK cells when interacting with their targets can gain antigens from them by the process of trogocytosis. Here we show that NK cells can obtain CCR5 and CXCR4, but barely CD4, from T cell lines by trogocytosis in vitro. By UMAP (Uniform Manifold Approximation and Projection), we show that aviremic HIV-1 patients have unique NK cell clusters that include cells expressing CCR5, NKG2C and KIRs, but lack CD57 expression. Viremic patients have a larger proportion of CXCR4 and CCR5 NK cells than healthy donors (HD) and this is largely increased in CD107 cells, suggesting a link between degranulation and trogocytosis. In agreement, UMAP identified a specific NK cell cluster in viremic HIV-1 patients, which contains most of the CD107a, CCR5 and CXCR4 cells. However, this cluster lacks NKG2C expression. Therefore, NK cells can gain CCR5 and CXCR4 by trogocytosis, which depends on degranulation.
自然杀伤（NK）细胞在抗病毒免疫反应中发挥着重要作用，包括对抗人类免疫缺陷病毒1型（HIV-1）。HIV-1患者的NK细胞活性受损，CD56 NK细胞减少，CD56CD16亚群增加，最近有人提出，一群CD56NKG2CKIRCD57细胞代表抗病毒记忆NK细胞。抗逆转录病毒疗法（ART）部分恢复了该淋巴细胞谱系的功能活性。NK细胞在与靶细胞相互作用时，可通过胞啃作用从靶细胞获取抗原。在此，我们表明，在体外，NK细胞可通过胞啃作用从T细胞系获得CCR5和CXCR4，但几乎无法获得CD4。通过均匀流形近似和投影（UMAP）分析，我们发现，病毒血症阴性的HIV-1患者具有独特的NK细胞簇，其中包括表达CCR5、NKG2C和杀伤细胞免疫球蛋白样受体（KIR）的细胞，但缺乏CD57表达。病毒血症阳性患者的CXCR4和CCR5 NK细胞比例高于健康供体（HD），且在CD107细胞中这一比例大幅增加，提示脱颗粒与胞啃作用之间存在联系。同样，UMAP在病毒血症阳性的HIV-1患者中鉴定出一个特定的NK细胞簇，其中包含大多数CD107a、CCR5和CXCR4细胞。然而，该簇缺乏NKG2C表达。因此，NK细胞可通过胞啃作用获得CCR5和CXCR4，这一过程依赖于脱颗粒。
