具有调节性细胞表型的循环T细胞比例随HIV相关免疫激活而增加，并在抗逆转录病毒治疗期间保持高位。

Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy.

作者信息

Lim Andrew, Tan Dino, Price Patricia, Kamarulzaman Adeeba, Tan Hong-Yien, James Ian, French Martyn A

机构信息

School of Surgery and Pathology, University of Western Australia, Rear 50 Murray Street, Perth 6000, Western Australia.

出版信息

AIDS. 2007 Jul 31;21(12):1525-34. doi: 10.1097/QAD.0b013e32825eab8b.

DOI:10.1097/QAD.0b013e32825eab8b

PMID:17630546

Abstract

OBJECTIVE

To examine the relationships between blood CD4 natural regulatory T (Treg) cells, plasma HIV RNA level, CD4 T-cell count and immune activation in untreated HIV-infected patients and immunodeficient patients beginning antiretroviral therapy (ART), using a novel phenotype to define Treg cells (CD25CD127CD4). Data were compared with established Treg cell markers (FoxP3, CTLA-4 and GITR).

METHODS

Twenty-nine untreated HIV-infected patients with CD4 T-cell counts of < 300 or > 400/microl were compared in a cross-sectional study and 12 patients beginning combination ART with < 100 CD4 T cells/mul were followed for 1 year on therapy. Three- and four-colour flow cytometry was used to quantitate proportions of Treg cells.

RESULTS

In control donors and patients with high CD4 T-cell counts, 28-89% (median 60%) of CD25CD127CD4 cells were FoxP3, but < 10% expressed GITR or CTLA-4. Immunodeficient patients also had CD4-negative lymphocytes with the phenotype FoxP3CD127. Proportions of CD25CD127 cells and activated (HLA-DR) cells in the CD4 T-cell population were increased in patients with low CD4 T cell counts. The proportion of CD25CD127CD4 T cells correlated positively with plasma HIV RNA level and CD4 T-cell activation, but inversely with CD4 T-cell count. Longitudinal studies of 12 patients receiving ART in two distinct cohorts (Western Australia and Malaysia) showed that the proportion of CD25CD127CD4 cells decreased slightly over time, but remained above levels seen in non-HIV controls.

CONCLUSIONS

Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high after 1 year on ART.

摘要

目的

使用一种新型表型（CD25⁺CD127⁻CD4⁺）来定义调节性T细胞（Treg），研究未经治疗的HIV感染患者以及开始抗逆转录病毒治疗（ART）的免疫缺陷患者的血液CD4⁺自然调节性T细胞、血浆HIV RNA水平、CD4⁺T细胞计数与免疫激活之间的关系。将数据与既定的Treg细胞标志物（FoxP3、CTLA-4和糖皮质激素诱导的肿瘤坏死因子受体（GITR））进行比较。

方法

在一项横断面研究中，对29例未经治疗、CD4⁺T细胞计数<300或>400/μl的HIV感染患者进行比较，并对12例开始联合ART且CD4⁺T细胞<100/μl的患者进行为期1年的治疗随访。使用三色和四色流式细胞术对Treg细胞比例进行定量分析。

结果

在对照供体和CD4⁺T细胞计数高的患者中，28%-89%（中位数60%）的CD25⁺CD127⁻CD4⁺细胞为FoxP3⁺，但<10%表达GITR或CTLA-4。免疫缺陷患者也有具有FoxP3⁺CD127⁻表型的CD4⁻淋巴细胞。CD4⁺T细胞计数低的患者中，CD4⁺T细胞群体中CD25⁺CD127⁻细胞和活化（HLA-DR⁺）细胞的比例增加。CD25⁺CD127⁻CD4⁺T细胞比例与血浆HIV RNA水平和CD4⁺T细胞活化呈正相关，但与CD4⁺T细胞计数呈负相关。对在两个不同队列（西澳大利亚和马来西亚）接受ART的12例患者进行的纵向研究表明，CD25⁺CD127⁻CD4⁺细胞比例随时间略有下降，但仍高于非HIV对照者的水平。