Adams Philipp, Fievez Virginie, Schober Rafaëla, Amand Mathieu, Iserentant Gilles, Rutsaert Sofie, Dessilly Géraldine, Vanham Guido, Hedin Fanny, Cosma Antonio, Moutschen Michel, Vandekerckhove Linos, Seguin-Devaux Carole
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg.
Department of Biomedical and Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium.
iScience. 2020 Nov 30;24(1):101881. doi: 10.1016/j.isci.2020.101881. eCollection 2021 Jan 22.
CD32 has raised conflicting results as a putative marker of the HIV-1 reservoir. We measured CD32 expression in tissues from viremic and virally suppressed humanized mice treated relatively early or late after HIV-1 infection with combined antiretroviral therapy. CD32 was expressed in a small fraction of the memory CD4 T-cell subsets from different tissues in viremic and aviremic mice, regardless of treatment initiation time. CD32 memory CD4 T cells were enriched in cell-associated (CA) HIV-1 DNA but not in CA HIV-1 RNA as compared to the CD32CD4 fraction. Using multidimensional reduction analysis, several memory CD4CD32 T-cell clusters were identified expressing HLA-DR, TIGIT, or PD-1. Importantly, although tissue-resident CD32CD4 memory cells were enriched with translation-competent reservoirs, most of it was detected in memory CD32CD4 T cells. Our findings support that CD32 labels highly activated/exhausted memory CD4 T-cell subsets that contain only a small proportion of the translation-competent reservoir.
作为HIV-1储存库的一种假定标志物,CD32产生了相互矛盾的结果。我们检测了在HIV-1感染后相对早期或晚期接受联合抗逆转录病毒治疗的病毒血症和病毒抑制的人源化小鼠组织中CD32的表达。无论治疗开始时间如何,CD32在病毒血症和无病毒血症小鼠不同组织的一小部分记忆CD4 T细胞亚群中表达。与CD32-CD4部分相比,CD32记忆CD4 T细胞在细胞相关(CA)HIV-1 DNA中富集,但在CA HIV-1 RNA中不富集。使用多维降维分析,鉴定出几个表达HLA-DR、TIGIT或PD-1的记忆CD4+CD32 T细胞簇。重要的是,尽管组织驻留CD32+CD4记忆细胞富含具有翻译能力的储存库,但其中大部分在记忆CD32-CD4 T细胞中检测到。我们的研究结果支持CD32标记高度活化/耗竭的记忆CD4 T细胞亚群,这些亚群仅包含一小部分具有翻译能力的储存库。