CEA-Université Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases (IMVA), IDMIT Department, IBFJ, DRF, Fontenay-aux-Roses, France.
Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne et Immunologie Clinique, Groupe Hospitalier Universitaire Paris Sud, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
Front Immunol. 2018 Jun 4;9:1217. doi: 10.3389/fimmu.2018.01217. eCollection 2018.
CD32a has been proposed as a specific marker of latently HIV-infected CD4 T cells. However, CD32a was recently found to be expressed on CD4 T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a CD4 T cells during HIV infection. To this end, we analyzed CD32a CD4 T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART) and in healthy donors. We found that CD32a CD4 T cells include heterogeneous subsets that are differentially affected by HIV infection. Our analysis revealed that naive (), central memory (), and effector/memory () CD32a CD4 T-cell clusters that co-express LILRA2- and CD64-activating receptors were more abundant in primary HIV infection and cART stages. Conversely, LILRA2 CD32a CD4 T-cell clusters of either the T, T, or T phenotype were more abundant in healthy individuals. Finally, an activated CD32a CD4 T cell cluster co-expressing LILRA2, CD57, and NKG2C was more abundant in all HIV stages, particularly during primary HIV infection. Overall, our data show that multiple abundance modifications of CD32a CD4 T-cell subsets occur in the early phase of HIV infection, and some of which are conserved after effective cART. Our study brings a better comprehension of the relationship between CD32a expression and CD4 T cells during HIV infection.
CD32a 被提议作为潜伏感染 HIV 的 CD4 T 细胞的特异性标志物。然而,最近发现 CD32a 也在健康供体的 CD4 T 细胞上表达,这导致了该标志物在 HIV 持续存在中的相关性存在争议。在这里,我们使用质谱流式细胞术来描述 HIV 感染过程中 CD32a+CD4 T 细胞的丰度变化。为此,我们分析了原发性 HIV 感染患者在接受有效联合抗逆转录病毒治疗(cART)前后以及健康供体的 CD32a+CD4 T 细胞。我们发现 CD32a+CD4 T 细胞包括异质性亚群,这些亚群受 HIV 感染的影响不同。我们的分析表明,幼稚()、中央记忆()和效应/记忆()CD32a+CD4 T 细胞簇,其共同表达 LILRA2 和 CD64 激活受体,在原发性 HIV 感染和 cART 阶段更为丰富。相反,LILRA2+CD32a+CD4 T 细胞簇,无论其表型是 T、T 还是 T,在健康个体中更为丰富。最后,一个表达 LILRA2、CD57 和 NKG2C 的活化 CD32a+CD4 T 细胞簇在所有 HIV 阶段都更为丰富,尤其是在原发性 HIV 感染期间。总体而言,我们的数据表明,在 HIV 感染的早期阶段,CD32a+CD4 T 细胞亚群的多个丰度修饰发生,其中一些在有效的 cART 后仍得以保留。我们的研究为理解 CD32a 表达与 HIV 感染期间 CD4 T 细胞之间的关系提供了更好的认识。