Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, Gansu 730050, P.R. China.
Department of Stress Medicine, Institute of Basic Medical Sciences, Beijing 100039, P.R. China.
Int J Mol Med. 2014 Feb;33(2):431-40. doi: 10.3892/ijmm.2013.1584. Epub 2013 Dec 11.
In this study, we aimed to measure P-glycoprotein (P-gp) expression in CD8(+) T lymphocytes of HIV-1-infected patients, to investigate how P-gp levels are affected by antiretroviral therapy (ART) in HIV-1 infection, and to assess the value of using P-gp expression to predict virologic response to ART. Peripheral blood mononuclear cells (PBMCs) were obtained from a cohort of HIV-1‑infected patients in China: 140 patients on ART, and 49 ART-naïve patients. We also enrolled 24 healthy blood donors as the controls. The expression levels of P-gp in CD8(+) T cells of HIV-1-infected patients were evaluated by quantitative reverse transcription PCR, ELISA and flow cytometry. A high inter-individual variability was observed in the CD8(+) T cells of both HIV-1-infected patients and healthy donors; however, the expression levels of P-gp were significantly higher in the HIV-1-infected group on ART compared to the ART-naïve group. The relative proportion of P-gp(+)CD8(+) T cells inversely correlated with the blood CD4(+) T cell count in the HIV-1‑infected patients on ART (r=-0.3343, P=0.0375). Groups of both good and poor responders showed significantly elevated levels of P-gp(+)CD8(+) T cells. The percentage of P-gp(+)CD8(+) T cells appeared to provide a sensitive estimate of the virologic response to ART compared to the CD4(+) T cell count. Our results suggest that P-gp expression varies among HIV-1‑infected patients, but is significantly higher in HIV-1‑infected patients on ART. The overexpression of P-gp is involved in ART initiation during HIV-1 infection, and P-gp(+)CD8(+) T cells may be an additional criterion for the evaluation of the antiretroviral response to ART.
在这项研究中,我们旨在测量 HIV-1 感染患者 CD8+T 淋巴细胞中的 P-糖蛋白(P-gp)表达,探讨 P-gp 水平如何受 HIV-1 感染中的抗逆转录病毒治疗(ART)影响,并评估使用 P-gp 表达来预测对 ART 的病毒学反应的价值。我们从中国的一组 HIV-1 感染患者中获得外周血单核细胞(PBMC):140 名接受 ART 的患者和 49 名未经 ART 的患者。我们还招募了 24 名健康献血者作为对照。通过定量逆转录 PCR、ELISA 和流式细胞术评估 HIV-1 感染患者 CD8+T 细胞中 P-gp 的表达水平。HIV-1 感染患者和健康供体的 CD8+T 细胞中观察到个体间存在高度变异性;然而,接受 ART 的 HIV-1 感染组的 P-gp 表达水平明显高于未经 ART 的组。接受 ART 的 HIV-1 感染患者中 P-gp(+)CD8+T 细胞的相对比例与血液 CD4+T 细胞计数呈负相关(r=-0.3343,P=0.0375)。良好和不良反应者组均显示 P-gp(+)CD8+T 细胞水平显著升高。与 CD4+T 细胞计数相比,P-gp(+)CD8+T 细胞的百分比似乎提供了对 ART 病毒学反应的敏感估计。我们的结果表明,P-gp 表达在 HIV-1 感染患者中存在差异,但在接受 ART 的 HIV-1 感染患者中明显升高。P-gp 的过度表达参与 HIV-1 感染期间的 ART 启动,P-gp(+)CD8+T 细胞可能是评估对 ART 的抗逆转录病毒反应的另一个标准。