Table_1_The Architecture of Circulating Immune Cells Is Dysregulated in People Living With HIV on Long Term Antiretroviral Treatment and Relates With Markers of the HIV-1 Reservoir, Cytomegalovirus, and Microbial Translocation.xlsx

Long-term changes in the immune system of successfully treated people living with HIV (PLHIV) remain incompletely understood. In this study, we assessed 108 white blood cell (WBC) populations in a cohort of 211 PLHIV on stable antiretroviral therapy and in 56 HIV-uninfected controls using flow cytometry. We show that marked differences exist in T cell maturation and differentiation between PLHIV and HIV-uninfected controls: PLHIV had reduced percentages of CD4+ T cells and naïve T cells and increased percentages of CD8+ T cells, effector T cells, and T helper 17 (Th17) cells, together with increased Th17/regulatory T cell (Treg) ratios. PLHIV also exhibited altered B cell maturation with reduced percentages of memory B cells and increased numbers of plasmablasts. Determinants of the T and B cell composition in PLHIV included host factors (age, sex, and smoking), markers of the HIV reservoir, and CMV serostatus. Moreover, higher circulating Th17 percentages were associated with higher plasma concentrations of interleukin (IL) 6, soluble CD14, the gut homing chemokine CCL20, and intestinal fatty acid binding protein (IFABP). The changes in circulating lymphocytes translated into functional changes with reduced interferon (IFN)- γ responses of peripheral blood mononuclear cells to stimulation with Candida albicans and Mycobacterium tuberculosis. In conclusion, this comprehensive analysis confirms the importance of persistent abnormalities in the number and function of circulating immune cells in PLHIV on stable treatment.

针对接受成功抗病毒治疗的人类免疫缺陷病毒（HIV）感染者（PLHIV，People Living with HIV）的免疫系统长期变化，目前仍未得到充分阐明。本研究采用流式细胞术（flow cytometry），对211名接受稳定抗逆转录病毒治疗的HIV感染者以及56名HIV阴性对照者的108种白细胞（white blood cell, WBC）群体进行了评估分析。研究结果显示，HIV感染者与HIV阴性对照者的T细胞成熟与分化状态存在显著差异：HIV感染者的CD4阳性T细胞、初始T细胞占比降低，而CD8阳性T细胞、效应T细胞以及辅助性T细胞17（Th17）占比升高，同时辅助性T细胞17/调节性T细胞（Treg）比值升高。HIV感染者还表现出B细胞成熟异常，具体为记忆B细胞占比降低、浆母细胞数量升高。影响HIV感染者T、B细胞组成的因素包括宿主因素（年龄、性别与吸烟史）、HIV病毒库标志物以及巨细胞病毒（CMV，Cytomegalovirus）血清学状态。此外，循环中较高的Th17细胞占比与白细胞介素6（IL-6）、可溶性CD14、肠道归巢趋化因子CCL20以及肠道脂肪酸结合蛋白（IFABP）的血浆浓度升高呈显著相关。循环淋巴细胞的上述改变可转化为免疫功能异常：外周血单个核细胞针对白色念珠菌（Candida albicans）与结核分枝杆菌（Mycobacterium tuberculosis）刺激产生的干扰素γ（IFN-γ）应答水平显著降低。综上，本项全面分析证实，在接受稳定抗逆转录病毒治疗的HIV感染者体内，循环免疫细胞的数量与功能仍持续存在异常，这一现象具有重要意义。