Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-α-producing antigen-presenting cells
Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-α-producing antigen-presenting cells
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DOI：
10.1002/art.23268
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发表时间：
2008-03-01
影响因子：
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通讯作者：
Chen, Shunle
中科院分区：
文献类型：
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作者：
Yan, Bing;Ye, Shuang;Chen, Shunle
Objective.目的探讨未经治疗的活动期系统性红斑狼疮（SLE）患者外周血中是否存在影响CD 4+、CD 25+调节性T细胞抑制功能的外在因素。我们研究了15例未经治疗的活动性SLE患者，10例缓解期SLE患者和15例健康对照者。流式细胞术检测CD 4+、CD 25+、FoxP 3 + Treg细胞的数量及FoxP 3蛋白水平。通过实时聚合酶链反应分析评估纯化的Treg细胞群中FoxP 3的信使RNA（mRNA）的表达。检测SLE中Treg细胞功能的实验旨在区分原发性和继发性T细胞功能障碍。用干扰素刺激的反应元件-荧光素酶报告基因测定法测定来自功能测定的上清液中干扰素-α（IFN α）的水平。SLE患者外周血中CD 4+、CD 25+、FoxP 3+细胞百分比显著高于对照组（平均值± SEM 9.11 ± 0.73%比4.78 ± 0.43%; P < 0.0001）。我们发现SLE患者与对照组相比，FoxP 3在任何CD 4+、CD 25 + T细胞亚群中的mRNA或蛋白水平表达均无差异。来自SLE患者的抗原呈递细胞（APC）负责降低Treg细胞活性，并且还可以使来自健康对照受试者的Treg细胞功能失调。来自SLE患者的CD 4+、CD 25 + Treg细胞在与来自健康对照的A-PC一起培养时表现出正常的抑制活性。SLE患者APC来源的高水平IFNa可诱导部分Treg细胞阻滞效应。我们认为，阻断Treg细胞介导的抑制IFN α产生的APC在SLE患者可能有助于在这种疾病的外周耐受性的致病性损失。
Objective. To explore whether there are extrinsic factors that impair the suppressive function of CD4+,CD25+ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE).Methods. We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4+,CD25+, FoxP3+ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-alpha (IFN alpha) in supernatants from the function assays were determined with an IFN-stimulated response element-luciferase reporter assay.Results. The percentage of CD4+,CD25+, FoxP3+ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean +/- SEM 9.11 +/- 0.73% versus 4.78 +/- 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4+,CD25+ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4+,CD25+ Treg cells from SLE patients exhibited normal suppressive activity when cultured with A-PCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFNa derived from SLE patient APCs.Conclusion. We suggest that blockade of Treg cell-mediated suppression by IFN alpha-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease.