Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Department of Central Laboratory, The Second Part of First Hospital, Jilin University, Changchun, China.
Clin Exp Immunol. 2013 Dec;174(3):345-55. doi: 10.1111/cei.12189.
The aim of this study was to examine the numbers of CD4(+) CD25(-) forkhead box protein 3 (FoxP3)(+) , CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells in patients with new-onset systemic lupus erythematosus (SLE). The numbers of CD4(+) CD25(-) FoxP3(+) , CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells and the concentrations of serum interleukin (IL)-10 in 23 patients and 20 healthy controls (HC) were measured. The potential correlations between CD4(+) FoxP3(+) T cells, serum IL-10 and clinical measures in SLE patients were analysed. In comparison with that in the HC, significantly reduced numbers of CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells, but increased numbers of CD4(+) CD25(-) FoxP3(+) T cells, were detected, accompanied by significantly lower levels of serum IL-10 in the patients. Stratification analysis indicated the numbers of CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells and serum IL-10 levels in the patients with seropositive anti-dsDNA were significantly less than that in those with seronegative anti-dsDNA. Treatment with the anti-SLE therapy, particularly with prednisone, leflunomide and methotrexate, significantly improved the imbalance of these types of FoxP3(+) T cells and increased the concentrations of serum IL-10 in the drug-responding patients. The numbers of CD4(+) CD25(+) FoxP3(+) T cells were correlated negatively with the values of SLE disease activity index (SLEDAI), whereas the numbers of CD4(+) CD25(-) FoxP3(+) T cells were correlated positively with the values of SLEDAI, erythrocyte sedimentation rate (ESR) and serum C3. In addition, the concentrations of serum IL-10 were correlated positively with the numbers of CD4(+) CD25(+) FoxP3(+) T cells, but negatively with the values of SLEDAI, serum C3, CRP and ESR in these patients. Our data indicate that the imbalance of different types of FoxP3(+) CD4(+) T cells may contribute to the development of SLE in Chinese patients.
本研究旨在检测初诊系统性红斑狼疮(SLE)患者外周血中 CD4+CD25-FoxP3+、CD4+CD25+FoxP3+和 CD4+CXCR5+FoxP3+T 细胞的数量,并探讨其与临床指标的相关性。我们采用流式细胞术检测了 23 例 SLE 患者和 20 例健康对照者外周血 CD4+FoxP3+T 细胞、血清白介素(IL)-10 水平,分析了 SLE 患者外周血 CD4+FoxP3+T 细胞与血清 IL-10 水平及临床指标的相关性。结果显示,与健康对照者相比,SLE 患者外周血 CD4+CD25+FoxP3+和 CD4+CXCR5+FoxP3+T 细胞数量显著减少,而 CD4+CD25-FoxP3+T 细胞数量显著增加,血清 IL-10 水平明显降低。进一步分层分析发现,血清抗双链 DNA(dsDNA)抗体阳性的 SLE 患者外周血 CD4+CD25+FoxP3+和 CD4+CXCR5+FoxP3+T 细胞数量及血清 IL-10 水平明显低于抗体阴性者。经抗 SLE 治疗后,特别是应用泼尼松、来氟米特和甲氨蝶呤治疗后,药物有效组患者上述 FoxP3+T 细胞亚群失衡状态得到改善,血清 IL-10 水平升高。同时,SLE 患者外周血 CD4+CD25+FoxP3+T 细胞数量与 SLE 疾病活动指数(SLEDAI)评分呈负相关,而 CD4+CD25-FoxP3+T 细胞数量与 SLEDAI 评分、红细胞沉降率(ESR)和血清补体 3(C3)呈正相关。此外,血清 IL-10 水平与 CD4+CD25+FoxP3+T 细胞数量呈正相关,与 SLEDAI 评分、血清 C3、C 反应蛋白(CRP)和 ESR 呈负相关。本研究表明,不同类型 FoxP3+CD4+T 细胞亚群失衡可能与中国 SLE 患者的发病有关。