Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy
Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy
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DOI：
10.1097/qad.0b013e32825eab8b
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发表时间：
2007-07-31
期刊：
影响因子：
3.8
通讯作者：
French, Martyn A.
中科院分区：
文献类型：
--
作者：
Lim, Andrew;Tan, Dino;French, Martyn A.
目的：探讨未经治疗的HIV感染患者和开始抗逆转录病毒治疗（ART）的免疫缺陷患者血液CD4自然调节性T细胞（T-reg）、血浆HIV RNA水平、CD4 T细胞计数和免疫激活之间的关系，使用一种新的表型来定义Treg细胞（CD25CD127(lo)CD4）。将数据与已建立的t - regg细胞标志物（FoxP3、CTLA-4和GITR）进行比较。方法：在一项横断面研究中比较了29例CD4 T细胞计数< 300或> 400/ μ l的未经治疗的hiv感染者，并对12例开始联合抗逆转录病毒治疗且CD4 T细胞计数< 100 / μ l的患者进行了1年的治疗随访。采用三色和四色流式细胞术定量测定Treg细胞的比例。结果：在对照供者和CD4 t细胞计数高的患者中，28-89%（中位数60%）的CD25CD127(lo)CD4细胞为FoxP3，但< 10%表达GITR或CTLA-4。免疫缺陷患者也有cd4阴性淋巴细胞，表型为FoxP3CD127（lo）。CD4 T细胞计数低的患者CD4 T细胞群中CD25CD127（lo）细胞和活化（HLA-DRhi）细胞的比例增加。CD25CD127(lo)CD4 T细胞比例与血浆HIV RNA水平和CD4 T细胞活化呈正相关，与CD4 T细胞计数呈负相关。在两个不同的队列（西澳大利亚和马来西亚）中对12名接受抗逆转录病毒治疗的患者进行的纵向研究表明，CD25CD127(lo)CD4细胞的比例随着时间的推移略有下降，但仍高于非hiv对照组的水平。结论：具有调节性细胞表型的循环T细胞比例随着hiv相关免疫激活而增加，并在ART治疗一年后保持较高水平。(c) 2007年Lippincott Williams & Wilkins。
Objective: To examine the relationships between blood CD4 natural regulatory T (T-reg) 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 (CD25CD127(lo)CD4). Data were compared with established T-reg cell markers (FoxP3, CTLA-4 and GITR).Methods: Twenty-nine untreated HIV-infected patients with CD4 T-cell counts of < 300 or > 400/mu l were compared in a cross-sectional study and 12 patients beginning combination ART with < 100 CD4 T cells/mu l 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 CD25CD127(lo)CD4 cells were FoxP3, but < 10% expressed GITR or CTLA-4. Immunodeficient patients also had CD4-negative lymphocytes with the phenotype FoxP3CD127(lo). Proportions of CD25CD127(lo) cells and activated (HLA-DRhi) cells in the CD4 T-cell population were increased in patients with low CD4 T cell counts. The proportion of CD25CD127(lo)CD4 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 CD25CD127(lo)CD4 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 I year on ART. (c) 2007 Lippincott Williams & Wilkins.