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肠道归巢 CD4+T 细胞亚群失衡与 HIV-1 感染的中国患者。

Imbalances of gut-homing CD4+ T-cell subsets in HIV-1-infected Chinese patients.

机构信息

HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Key Clinical Department of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.

出版信息

J Acquir Immune Defic Syndr. 2013 Sep 1;64(1):25-31. doi: 10.1097/QAI.0b013e318293a114.

Abstract

BACKGROUND

Full reconstitution of CD4 T cells in both peripheral blood and mucosal tissues is a desirable goal of treating AIDS patients. To date, few studies have investigated the potential role of gut-homing CD4 T-cell subsets as biomarkers in assisting Asian populations infected with HIV-1.

METHODS

A large cross-sectional study was conducted among Chinese patients with focus on the frequency, absolute number, and ratio of gut-homing Th1, Th17, and Treg subsets in 3 groups of age- and gender-matched study subjects: healthy donors, untreated AIDS patients, and antiretroviral therapy (ART)-treated patients with sustained undetectable viral load.

RESULTS

HIV-1 chronic infection resulted in positively correlated loss of total and gut-homing CD4 T cells (P < 0.001) among patients compared with healthy controls. Profiles of T-cell subsets, however, were different between total and gut-homing CD4 T cells in terms of frequency and absolute number. ART partially restored the frequencies of gut-homing Th1, Th17, and Treg cells but the lost number of gut-homing Th17 cells was found not easily reversible. These changes together with an increased frequency of gut-homing CD4 Treg cells led to dual imbalances of gut-homing Th1/Treg and Th17/Treg ratios, which were negatively correlated with viral load (P = 0.014 and P < 0.001) and hardly restored even by prolonged ART.

CONCLUSIONS

Our findings provide new insights into the investigation of gut-homing Th1/Treg and Th17/Treg imbalances in AIDS patients, which may have potential implications on the reconstitution of mucosal CD4 T cells.

摘要

背景

在外周血和黏膜组织中完全重建 CD4 T 细胞是治疗 AIDS 患者的理想目标。迄今为止,很少有研究调查肠道归巢 CD4 T 细胞亚群作为辅助 HIV-1 感染亚洲人群的生物标志物的潜在作用。

方法

对中国患者进行了一项大型横断面研究,重点关注 3 组年龄和性别匹配的研究对象中肠道归巢 Th1、Th17 和 Treg 亚群的频率、绝对数量和比例:健康供体、未接受治疗的 AIDS 患者和接受抗逆转录病毒治疗(ART)且病毒载量持续不可检测的患者。

结果

与健康对照组相比,HIV-1 慢性感染导致患者总 CD4 和肠道归巢 CD4 T 细胞呈正相关丢失(P<0.001)。然而,T 细胞亚群的特征在总 CD4 和肠道归巢 CD4 T 细胞方面在频率和绝对数量上有所不同。ART 部分恢复了肠道归巢 Th1、Th17 和 Treg 细胞的频率,但肠道归巢 Th17 细胞的丢失数量不易恢复。这些变化加上肠道归巢 CD4 Treg 细胞频率的增加导致肠道归巢 Th1/Treg 和 Th17/Treg 比值的双重失衡,这与病毒载量呈负相关(P=0.014 和 P<0.001),即使通过延长 ART 也难以恢复。

结论

我们的研究结果为研究 AIDS 患者肠道归巢 Th1/Treg 和 Th17/Treg 失衡提供了新的见解,这可能对黏膜 CD4 T 细胞的重建具有潜在意义。

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