Cao Qing-hua, Xue Yi-le, Wang Ying
AIDS/STD Department, Shanghai Municipal Center for Disease Control & Prevention/Shanghai Municipal Institute of Preventive Medicine, Shanghai 200336, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009 Nov;25(11):1020-2.
To investigate whether Programmed death-1 (PD-1) expression on peripheral CD4(+)CD25(nt/hi)CD127(lo) regulatory T cells (Treg) was associated with disease progression in HIV-1-infected patients.
Peripheral blood from 108 HIV-1-infected patients in distinct disease progression statuses and 27 healthy individuals were collected in the present investigation. PBMCs were isolated by centrifugation on Ficoll-Hypaque, followed by staining with anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE and anti-PD-1-APC. PD-1 expression on Treg was analyzed by four-color staining flow cytometry. CD4(+) T cell absolute counts were determined using Multitest CD3/CD4/CD8/CD45 kit and plasma viral loads were detected on NucliSens EasyQ. All data were analyzed using SPSS14.0 software.
In peripheral blood of healthy individuals, Treg expressed PD-1 at very low levels (1.72%+/-0.65%). In contrast, Treg from HIV-1-infected patients showed a significantly increased PD-1 expression (5.33%+/-2.24%, P<0.01). Moreover, AIDS patients exhibited statistically higher PD-1 expression on Treg (7.87%+/-2.23%) than newly HIV-1 infected patients (3.22%+/-1.01%, P<0.05) and patients in progression to AIDS(5.21%+/-1.72%, P<0.05). PD-1 up-regulation on Treg was closely correlated with reduced CD4(+) T cell absolute counts but elevated plasma viral load.
Overall, we found that PD-1 expression on peripheral Treg was up-regulated and correlated with disease progression in HIV-1-infected patients for the first time. These findings not only extend our understanding of how Treg functions in HIV-1-infected patients but also support the notion that blocking PD-1/PD-L1 interactions may represent a potential therapeutic strategy for HIV-1-infected patients.
研究外周血CD4(+)CD25(nt/hi)CD127(lo)调节性T细胞（Treg）上程序性死亡蛋白1（PD-1）的表达是否与HIV-1感染患者的疾病进展相关。
本研究收集了108例处于不同疾病进展状态的HIV-1感染患者及27名健康个体的外周血。通过Ficoll-Hypaque密度梯度离心法分离外周血单个核细胞（PBMC），随后用抗CD4-PerCP、抗CD25-FITC、抗CD127-PE和抗PD-1-APC进行染色。采用四色染色流式细胞术分析Treg上PD-1的表达。使用Multitest CD3/CD4/CD8/CD45试剂盒测定CD4(+) T细胞绝对计数，并在NucliSens EasyQ上检测血浆病毒载量。所有数据均使用SPSS14.0软件进行分析。
在健康个体外周血中，Treg上PD-1表达水平极低（1.72%±0.65%）。相比之下，HIV-1感染患者的Treg上PD-1表达显著增加（5.33%±2.24%，P<0.01）。此外，艾滋病患者Treg上的PD-1表达在统计学上高于新感染HIV-1的患者（3.22%±1.01%，P<0.05）以及进展为艾滋病的患者（5.21%±1.72%，P<0.05）。Treg上PD-1上调与CD4(+) T细胞绝对计数减少但血浆病毒载量升高密切相关。
总体而言，我们首次发现HIV-1感染患者外周Treg上的PD-1表达上调且与疾病进展相关。这些发现不仅扩展了我们对HIV-1感染患者中Treg功能的理解，也支持了阻断PD-1/PD-L1相互作用可能代表HIV-1感染患者潜在治疗策略的观点。
