Institut Pasteur, Unité HIV Inflammation et Persistance, Paris, France.
Institut Pasteur, Hub Bioinformatique et Biostatistique, Paris, France.
Nat Metab. 2019 Jul;1(7):704-716. doi: 10.1038/s42255-019-0081-4. Epub 2019 Jul 12.
Spontaneous control of human immunodeficiency virus (HIV) is generally associated with an enhanced capacity of CD8 T cells to eliminate infected CD4 T cells, but the molecular characteristics of these highly functional CD8 T cells are largely unknown. In the present study, using single-cell analysis, it was shown that HIV-specific, central memory CD8 T cells from spontaneous HIV controllers (HICs) and antiretrovirally treated non-controllers have opposing transcriptomic profiles. Genes linked to effector functions and survival are upregulated in cells from HICs. In contrast, genes associated with activation, exhaustion and glycolysis are upregulated in cells from non-controllers. It was shown that HIV-specific CD8 T cells from non-controllers are largely glucose dependent, whereas those from HICs have more diverse metabolic resources that enhance both their survival potential and their capacity to develop anti-HIV effector functions. The functional efficiency of the HIV-specific CD8 T cell response in HICs is thus engraved in their memory population and related to their metabolic programme. Metabolic reprogramming in vitro through interleukin-15 treatment abrogated the glucose dependency and enhanced the antiviral potency of HIV-specific CD8 T cells from non-controllers.
人体免疫缺陷病毒 (HIV) 的自发控制通常与 CD8 T 细胞消除感染的 CD4 T 细胞的能力增强有关，但这些高功能 CD8 T 细胞的分子特征在很大程度上尚不清楚。在本研究中，通过单细胞分析表明，来自自发 HIV 控制器 (HIC) 和接受抗逆转录病毒治疗的非控制器的 HIV 特异性中央记忆 CD8 T 细胞具有相反的转录组特征。与效应功能和存活相关的基因在 HIC 细胞中上调。相比之下，与激活、衰竭和糖酵解相关的基因在非控制器的细胞中上调。研究表明，非控制器的 HIV 特异性 CD8 T 细胞在很大程度上依赖于葡萄糖，而 HIC 中的 HIV 特异性 CD8 T 细胞具有更多样化的代谢资源，这增强了它们的存活潜力和产生抗 HIV 效应功能的能力。因此，HIC 中 HIV 特异性 CD8 T 细胞反应的功能效率铭刻在其记忆群体中，并与它们的代谢程序相关。通过白细胞介素-15 治疗进行体外代谢重编程消除了葡萄糖依赖性，并增强了非控制器的 HIV 特异性 CD8 T 细胞的抗病毒效力。
