CEA-Université Paris-Saclay-INSERM U1184, Immunology of Viral Infections, Autoimmune, Hematological and Bacterial diseases, (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
AP-HP, Laboratoire de Microbiologie Clinique, Hôpital Necker-Enfants Malades, Paris, France.
Eur J Immunol. 2021 Aug;51(8):2040-2050. doi: 10.1002/eji.202048943. Epub 2021 Jun 7.
New ways of characterizing CD8 memory T cell responses in chronic infections are based on the measurement of chemokine receptor expression (CXCR3, CXCR5, and CX3CR1). We applied these novel phenotyping strategies to chronic HIV infection by comparing healthy donors (HDs), HIV-infected patients receiving antiretroviral therapy (ART), and spontaneous HIV controllers (HICs). In all groups, the memory cells exhibited high proportion of CXCR3 cells. Proportions of CXCR5 and CX3CR1 cells were preferentially observed among central memory cells (Tcm) and effector memory cells (Tem) respectively. Chronic controlled HIV infection impacted the chemokine receptor profile of both HIV-specific and nonspecific CD8 T cells. In total CD8 T cells, the proportions of CXCR3 CXCR5 CX3CR1 Tcm and Tem were lower in HIV-infected patients than in HDs with subtle differences between ART and HICs. Such phenotyping strategy also revealed differences in exhaustion and senescence phenotypes, the CXCR3 CXCR5 CX3CR1 being more exhausted and senescent than the CXCR3 CXCR5 CX3CR1 Tcm fraction. Among HIV-specific CD8 T cells, the vast majority of Tcm cells were CXCR3 and CXCR5 cells in contrast with their nonspecific counterparts. In conclusion, the addition of migration markers contributes to better characterize Tcm/Tem compartment.
新的方法来描述慢性感染中的 CD8 记忆 T 细胞反应是基于趋化因子受体表达(CXCR3、CXCR5 和 CX3CR1)的测量。我们通过比较健康供体(HDs)、接受抗逆转录病毒治疗(ART)的 HIV 感染患者和自发 HIV 控制器(HICs),将这些新的表型策略应用于慢性 HIV 感染。在所有组中,记忆细胞表现出高比例的 CXCR3 细胞。CXCR5 和 CX3CR1 细胞的比例分别优先出现在中央记忆细胞(Tcm)和效应记忆细胞(Tem)中。慢性控制的 HIV 感染影响了 HIV 特异性和非特异性 CD8 T 细胞的趋化因子受体谱。在总 CD8 T 细胞中,与 HD 相比,感染 HIV 的患者中 CXCR3 CXCR5 CX3CR1 Tcm 和 Tem 的比例较低,ART 和 HIC 之间存在细微差异。这种表型策略还揭示了耗竭和衰老表型的差异,CXCR3 CXCR5 CX3CR1 比 CXCR3 CXCR5 CX3CR1 Tcm 更耗竭和衰老。在 HIV 特异性 CD8 T 细胞中,绝大多数 Tcm 细胞是 CXCR3 和 CXCR5 细胞,而不是它们的非特异性对应物。总之,添加迁移标记有助于更好地描述 Tcm/Tem 区室。