IgA 肾病患者扁桃体中的 CD4+CD25+调节性 T 细胞在实验性 IgA 肾病大鼠中具有降低的免疫抑制活性。
Tonsillar CD4+CD25+ regulatory T cells from IgA nephropathy patients have decreased immunosuppressive activity in experimental IgA nephropathy rats.
机构信息
Division of Nephrology, Beijing Shijitan Hospital, Capital Medical University, Beijing, PR China.
出版信息
Am J Nephrol. 2013;37(5):472-80. doi: 10.1159/000350533. Epub 2013 Apr 30.
BACKGROUND/AIM: CD4+CD25+ regulatory T (Treg) cells are of critical importance for maintenance of tolerance. We showed that the number of CD4+CD25+ Treg cells was significantly lower in tonsils of patients with IgA nephropathy (IgAN); however, the function of tonsillar CD4+CD25+ Treg cells in IgAN has not been reported. The aim of this study was to investigate the effect of tonsillar CD4+CD25+ Treg cells of IgAN patients on experimental IgAN in rats.
METHODS
Tonsillar CD4+CD25+ Treg cells were isolated by magnetic beads. A total of 2 × 10(6) CD4+CD25+ Treg cells were transferred into rats that were previously orally immunized over a period of 14 weeks and subsequently received an injection of BSA into the tail vein on 3 consecutive days. Urine protein and erythrocytes were measured. Glomerular injury was assessed by histopathology. Plasminogen activator inhibitor type 1 (PAI-1), interleukin (IL)-6 and transforming growth factor (TGF)-β1 in mesangial cells of rats were examined by reverse transcription PCR. Serum IgA and C3 and supernatants of IL-2, IL-4 and IL-6 in splenic cells were analysed by ELISA. Transferred tonsillar CD4+CD25+ Treg cells were tracked by reverse transcription PCR and flow cytometry.
RESULTS
IgA deposition in the mesangial region and the glomerular planar area and the number of cells, levels of serum IgA and supernatant IL-2, IL-4 and IL-6 in splenic cells and PAI-1, IL-6 and TGF-β1 expression in renal mesangial cells of rats that received CD4+CD25+ Treg cells from IgAN patients were significantly higher than in rats that received CD4+CD25+ Treg cells from the control group, although they were dramatically lower compared with rats treated without CD4+CD25+ Treg cells. Transferred tonsillar CD4+CD25+ Treg cells migrated predominantly to secondary lymphoid organs but not to the kidneys.
CONCLUSION
Dysfunction of tonsillar CD4+CD25+ Treg cells may be an important cause of IgAN progression.
背景/目的：CD4+CD25+调节性 T（Treg）细胞对于维持耐受至关重要。我们发现，IgA 肾病（IgAN）患者的扁桃体中 CD4+CD25+Treg 细胞数量明显较低；然而，IgAN 扁桃体 CD4+CD25+Treg 细胞的功能尚未报道。本研究旨在探讨 IgAN 患者扁桃体 CD4+CD25+Treg 细胞对大鼠实验性 IgAN 的影响。
方法
通过磁珠分离扁桃体 CD4+CD25+Treg 细胞。将总共 2×106 CD4+CD25+Treg 细胞转移到先前口服免疫 14 周的大鼠中，并随后在连续 3 天向尾静脉注射 BSA。测量尿蛋白和红细胞。通过组织病理学评估肾小球损伤。通过逆转录 PCR 检测大鼠系膜细胞中纤溶酶原激活物抑制剂 1（PAI-1）、白细胞介素（IL）-6 和转化生长因子（TGF）-β1。通过 ELISA 分析脾细胞上清液中血清 IgA 和 C3 以及 IL-2、IL-4 和 IL-6。通过逆转录 PCR 和流式细胞术追踪转移的扁桃体 CD4+CD25+Treg 细胞。
结果
接受来自 IgAN 患者的 CD4+CD25+Treg 细胞的大鼠系膜区和肾小球平面区 IgA 沉积以及细胞数量、血清 IgA 和脾细胞上清液中 IL-2、IL-4 和 IL-6 水平以及肾系膜细胞中 PAI-1、IL-6 和 TGF-β1 表达均明显高于接受来自对照组的 CD4+CD25+Treg 细胞的大鼠，但与未经 CD4+CD25+Treg 细胞治疗的大鼠相比显著降低。转移的扁桃体 CD4+CD25+Treg 细胞主要迁移到次级淋巴器官，而不是肾脏。
结论
扁桃体 CD4+CD25+Treg 细胞功能障碍可能是 IgAN 进展的重要原因。
Zotero 插件