Zhang B, Zhang X, Tang F, Zhu L, Liu Y
Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China.
Clin Exp Immunol. 2008 Aug;153(2):182-7. doi: 10.1111/j.1365-2249.2008.03686.x. Epub 2008 May 26.
The aim of this study was to quantify and evaluate the forkhead box P3 (FoxP3) expression regulatory T cells in new-onset systemic lupus erythematosus (SLE) patients before and after treatment. Forty-four newly diagnosed and untreated SLE patients, including 24 with active disease (SLEDAI > or = 10) and 20 with inactive disease (SLEDAI < 5), were enrolled in this study. Twenty-one age- and sex-matched healthy volunteers were also included as controls. Peripheral blood samples were collected and mononuclear cells isolated. The expression of CD25 and FoxP3 in CD4(+) T cells were analysed with flow cytometry. CD4(+)CD25(+) (3.95-13.04%) and CD4(+)CD25(high) (0.04-1.34%) T cells in peripheral blood in untreated patients with new-onset active lupus were significantly lower than that in the patients with inactive lupus (7.27-24.48%, P < 0.05 and 0.14-3.07% P < 0.01 respectively) and that in healthy controls (5.84-14.84%, P < 0.05). Interestingly, the decrease in CD4(+)CD25(high) T cells was restored significantly in patients with active lupus after corticosteroid treatment. There was, however, a significantly higher percentage of CD4(+)FoxP3(+) T cells in patients with active (5.30-23.00%) and inactive (7.46-17.38%) new-onset lupus patients compared with healthy control subjects (2.51-12.94%) (P < 0.01). Intriguingly, CD25 expression in CD4(+)FoxP3(+) T cells in patients with active lupus (25.24-62.47%) was significantly lower than that in those patients with inactive lupus (30.35-75.25%, P < 0.05) and healthy controls (54.83-86.38%, P < 0.01). Most strikingly, the levels of FoxP3 expression determined by mean fluorescence intensity in CD4(+)CD25(high) cells in patients with active SLE were significantly down-regulated compared with healthy subjects (130 +/- 22 versus 162 +/- 21, P = 0.012). CD4(+)CD25(high) T cells are low in new-onset patients with active SLE and restored after treatment. Despite that the percentage of CD4(+)FoxP3(+) T cells appear high, the levels of FoxP3 expression in CD4(+)CD25(high) T cells are down-regulated in untreated lupus patients. There is a disproportional expression between CD25(high) and FoxP3(+) in new-onset patients with active SLE.
本研究旨在对初发性系统性红斑狼疮（SLE）患者治疗前后的叉头框P3（FoxP3）表达调节性T细胞进行定量和评估。44例新诊断且未治疗的SLE患者纳入本研究，其中24例为活动期疾病（SLEDAI≥10），20例为非活动期疾病（SLEDAI＜5）。21例年龄和性别匹配的健康志愿者作为对照。采集外周血样本并分离单个核细胞。采用流式细胞术分析CD4(+)T细胞中CD25和FoxP3的表达。初发性活动期狼疮未治疗患者外周血中CD4(+)CD25(+)（3.95 - 13.04%）和CD4(+)CD25(high)（0.04 - 1.34%）T细胞显著低于非活动期狼疮患者（7.27 - 24.48%，P＜0.05；0.14 - 3.07%，P＜0.01）以及健康对照（5.84 - 14.84%，P＜0.05）。有趣的是，活动期狼疮患者经皮质类固醇治疗后，CD4(+)CD25(high)T细胞的减少显著恢复。然而，与健康对照受试者（2.51 - 12.94%）相比，活动期（5.30 - 23.00%）和非活动期（7.46 - 17.38%）初发性狼疮患者中CD4(+)FoxP3(+)T细胞的百分比显著更高（P＜0.01）。有趣的是，活动期狼疮患者CD4(+)FoxP3(+)T细胞中CD25的表达（25.24 - 62.47%）显著低于非活动期狼疮患者（30.35 - 75.25%，P＜0.05）和健康对照（54.83 - 86.38%，P＜0.01）。最显著的是，与健康受试者相比，活动期SLE患者CD4(+)CD25(high)细胞中通过平均荧光强度测定的FoxP3表达水平显著下调（130±22对162±21，P = 0.012）。初发性活动期SLE患者CD4(+)CD25(high)T细胞数量低，治疗后恢复。尽管CD4(+)FoxP3(+)T细胞百分比看似较高，但未治疗的狼疮患者CD4(+)CD25(high)T细胞中FoxP3表达水平下调。初发性活动期SLE患者中CD25(high)与FoxP3(+)之间存在不成比例的表达。
