The percentage of FoxP3+Helios+ Treg cells correlates positively with disease activity in systemic lupus erythematosus.

The percentage of FoxP3+Helios+ Treg cells correlates positively with disease activity in systemic lupus erythematosus.
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DOI:
10.1002/art.38119
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发表时间:
2013-11
影响因子:
--
通讯作者:
Shevach, Ethan M.
Shevach, Ethan M.
中科院分区:
其他
文献类型:
--
作者:
Golding, Amit;Hasni, Sarfaraz;Illei, Gabor;Shevach, Ethan M.

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评估Helios联合FoxP 3作为一种上级方法在系统性红斑狼疮(SLE)患者中鉴定不产生细胞因子的人Treg细胞,并确定FoxP 3 +Helios+ Treg细胞在临床活动性疾病患者中是否维持在正常水平。从健康志愿者供体和52名连续患有不同临床活动性(系统性红斑狼疮疾病活动指数评分为0、2-4和≥5)的SLE患者的血液中纯化外周血单核细胞(PBMC)。然后通过流式细胞术分析PBMC(新鲜或刺激4小时后的细胞因子产生)的细胞表面标志物(CD 4、CD 25、CD 127和CD 45 RA)和转录因子(FoxP 3和Helios)的表达以及细胞因子(白细胞介素-2和干扰素- γ)的产生。发现FoxP 3 +Helios+ Treg细胞在SLE患者和健康对照中均不产生细胞因子。临床活动性SLE患者的FoxP 3 +Helios+ Treg细胞百分比高于非活动性SLE患者或健康对照。当校正总CD 4细胞计数时,中度至高度活动性SLE患者中FoxP 3 +Helios+ Treg细胞的绝对数量正常。先前关于SLE中Treg细胞数量或功能缺陷的报道受到其单独或与其他标志物组合使用CD 25来鉴定人Treg细胞的限制。Helios联合FoxP 3是一种用于检测所有非细胞因子产生性Treg细胞的上级方法,无论CD 25或CD 45 RA表达如何。使用这种方法,我们表明FoxP 3 +Helios+ Treg细胞数量在临床活动性SLE患者中没有减少。
To assess the use of Helios in combination with FoxP3 as a superior method for identifying non–cytokine-producing human Treg cells in patients with systemic lupus erythematosus (SLE) and to determine if FoxP3+Helios+ Treg cells are maintained at normal levels in patients with clinically active disease. Peripheral blood mononuclear cells (PBMCs) were purified from the blood of healthy volunteer donors and from 52 consecutive patients with SLE of varying clinical activity (Systemic Lupus Erythematosus Disease Activity Index scores of 0, 2–4, and ≥5). PBMCs (either fresh or after 4 hours of stimulation for cytokine production) were then analyzed by flow cytometry for the expression of cell surface markers (CD4, CD25, CD127, and CD45RA) and transcription factors (FoxP3 and Helios), as well as for the production of cytokines (interleukin-2 and interferon- γ). FoxP3+Helios+ Treg cells were found to be non–cytokine producing in both SLE patients and healthy controls. Patients with clinically active SLE had higher percentages of FoxP3+Helios+ Treg cells than did patients with inactive SLE or healthy controls. When corrected for the total CD4 cell count, the absolute numbers of FoxP3+Helios+ Treg cells in patients with moderately-to-highly active SLE were normal. Previous reports of a deficiency in Treg cell number or function in SLE are limited by their use of CD25, either alone or in combination with other markers, to identify human Treg cells. Helios in combination with FoxP3 is a superior method for detecting all non–cytokine-producing Treg cells, irrespective of CD25 or CD45RA expression. Using this method, we showed that FoxP3+Helios+ Treg cell numbers are not reduced in patients with clinically active SLE.
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