Khoury Gabriela, Anderson Jenny L, Fromentin Rémi, Hartogenesis Wendy, Smith Miranda Z, Bacchetti Peter, Hecht Frederick M, Chomont Nicolas, Cameron Paul U, Deeks Steven G, Lewin Sharon R
aThe Peter Doherty Institute for Infection and Immunity, University of MelbournebDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, AustraliacDepartment of Microbiology, Infectiology and Immunology, Université de Montréal, Faculty of Medicine, and Centre de Recherche du CHUM, Montréal, Quebec, CanadadDepartment of MedicineeDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
AIDS. 2016 Jun 19;30(10):1511-20. doi: 10.1097/QAD.0000000000001029.
HIV latent infection can be established in vitro by treating resting CD4 T cells with chemokines that bind to chemokine receptors (CKR), CCR7, CXCR3, and CCR6, highly expressed on T cells.
To determine if CKR identify CD4 T cells enriched for HIV in HIV-infected individuals receiving suppressive antiretroviral therapy (ART).
A cross-sectional study of CKR expression and HIV persistence in blood from HIV-infected individuals on suppressive ART for more than 3 years (n = 48). A subset of 20 individuals underwent leukapheresis and sorting of specific CD4 T-cell subsets.
We used flow cytometry to quantify CCR5, CCR6, CXCR3, and CXCR5 expression on CD4 T cells. HIV persistence was quantified using real-time Polymerase Chain Reaction to detect total, integrated HIV DNA, 2-long terminal repeat circles and cell-associated unspliced (CA-US) HIV RNA in total CD4 T cells from blood or sorted T-cell subsets. Associations between CKR and HIV persistence in CD4 T cells in blood were determined using regression models and adjusted for current and nadir CD4 T-cell counts.
The frequency of cells harbouring integrated HIV DNA was inversely associated with current CD4 T-cell count and positively associated with CCR5+ CD4 T cells, CXCR3+CCR6+ and CXCR3+CCR6- expression on total memory CD4 T cells (P < 0.001, 0.048, 0.015, and 0.016, respectively). CXCR3+CCR6+ CM CD4 T cells contained the highest amount of integrated HIV DNA and lowest ratio of CA-US HIV RNA to DNA compared to all T-cell subsets examined.
CXCR3 and CCR6 coexpression defines a subset of CD4 T cells that are preferentially enriched for HIV DNA in HIV-infected individuals on ART.
通过用与趋化因子受体（CKR）、CCR7、CXCR3和CCR6结合的趋化因子处理静息CD4 T细胞，可在体外建立HIV潜伏感染，这些趋化因子受体在T细胞上高度表达。
确定在接受抑制性抗逆转录病毒疗法（ART）的HIV感染者中，CKR是否能识别富含HIV的CD4 T细胞。
一项横断面研究，对接受抑制性ART超过3年的HIV感染者（n = 48）血液中的CKR表达和HIV持续性进行研究。20名个体的一个亚组接受了白细胞分离术和特定CD4 T细胞亚群的分选。
我们使用流式细胞术对CD4 T细胞上的CCR5、CCR6、CXCR3和CXCR5表达进行定量。使用实时聚合酶链反应对HIV持续性进行定量，以检测血液中总CD4 T细胞或分选的T细胞亚群中的总整合HIV DNA、2-长末端重复序列环和细胞相关未剪接（CA-US）HIV RNA。使用回归模型确定血液中CD4 T细胞中CKR与HIV持续性之间的关联，并根据当前和最低点CD4 T细胞计数进行调整。
携带整合HIV DNA的细胞频率与当前CD4 T细胞计数呈负相关，与总记忆CD4 T细胞上的CCR5 + CD4 T细胞、CXCR3 + CCR6 +和CXCR3 + CCR6-表达呈正相关（P分别<0.001、0.048、0.015和0.016）。与所有检查的T细胞亚群相比，CXCR3 + CCR6 +中央记忆CD4 T细胞含有最高量的整合HIV DNA和最低的CA-US HIV RNA与DNA比率。
CXCR3和CCR6共表达定义了一个CD4 T细胞亚群，在接受ART的HIV感染者中，该亚群优先富集HIV DNA。
