Hunan Key Laboratory of Nephrology and Hemoperfusion, Division of Nephrology, Second Xiangya Hospital of Central South University, Changsha, Hunan Province - PR China.
J Nephrol. 2010 Mar-Apr;23(2):202-9.
The relationship between tonsillar autoimmune response and the pathogenesis of IgA nephropathy (IgAN) has been previously demonstrated. However, the role of CD4+CD25+ cells, which play critical roles in maintaining peripheral tolerance and preventing autoimmunity, has not yet been defined in IgAN.
The lymphocytes from tonsils of all subjects (including 37 IgAN cases and 37 controls without renal diseases) were cultured for 72 hours without stimulation, or with stimulation by alpha-hemolytic streptococcus (HS) isolated from the tonsillar crypts of cases (the HS-IgAN) or controls (HS-controls). The CD4+CD25+ cells were measured by flow cytometry. Expression of J chain mRNA was analyzed by in situ hybridization (ISH) and the dimeric IgA-producing cells were identified by immunofluorescence and fluorescent ISH.
The number of CD4+CD25+ cells was significantly lower in cases than in controls (0.98% +/- 0.204% vs. 3.58% +/- 0.554%, 1.37% +/- 0.214% vs. 5.78% +/- 0.562%, and 1.43% +/- 0.202% vs. 6.05% +/- 0.521%, for nonstimulation, HS-controls and HS-cases, respectively). CD4+CD25+ cells from cases showed a significantly lower stimulation index (SI) when stimulated with HS-controls and HS-IgAN than controls (p<0.05), whereas the number of dimeric IgA-producing cells was significantly higher in cases than controls (11.9% +/- 3.1% vs. 6.5% +/- 1.5%, 33.5% +/- 5.7% vs. 13.9% +/- 1.2%, and 35.1% +/- 6.2% vs. 13.9% +/- 1.2%, for nonstimulation, HS-controls and HS-cases, respectively). The dimeric IgA-producing cells from patients with IgAN showed a significantly higher SI when stimulated with HS-controls, or HS-IgAN than those from patients without renal disease (p<0.01). The SI of CD4+CD25+ cells was negatively correlated with that of dimeric IgA-producing cells.
The results suggest that CD4+CD25+ cells and dimeric IgA-producing cells in tonsils may be related to the pathogenesis of IgAN.
扁桃体自身免疫反应与 IgA 肾病（IgAN）发病机制之间的关系已得到证实。然而，在 IgAN 中，CD4+CD25+细胞（其在维持外周耐受和防止自身免疫中起关键作用）的作用尚未确定。
对所有受试者（包括 37 例 IgAN 患者和 37 例无肾脏疾病的对照者）的扁桃体淋巴细胞进行 72 小时无刺激培养，或用来自病例扁桃体隐窝的α-溶血性链球菌（HS）刺激（HS-IgAN）或对照者（HS-对照者）。用流式细胞术测定 CD4+CD25+细胞。用原位杂交（ISH）分析 J 链 mRNA 的表达，并用免疫荧光和荧光 ISH 鉴定二聚体 IgA 产生细胞。
与对照组相比，病例组的 CD4+CD25+细胞数明显减少（非刺激时分别为 0.98% +/- 0.204%比 3.58% +/- 0.554%，1.37% +/- 0.214%比 5.78% +/- 0.562%，和 1.43% +/- 0.202%比 6.05% +/- 0.521%）。与对照组相比，病例组 CD4+CD25+细胞在刺激 HS-对照者和 HS-IgAN 时的刺激指数（SI）明显降低（p<0.05），而病例组二聚体 IgA 产生细胞的数量明显高于对照组（非刺激时分别为 11.9% +/- 3.1%比 6.5% +/- 1.5%，33.5% +/- 5.7%比 13.9% +/- 1.2%，和 35.1% +/- 6.2%比 13.9% +/- 1.2%）。来自 IgAN 患者的二聚体 IgA 产生细胞在刺激 HS-对照者或 HS-IgAN 时的 SI 明显高于无肾脏疾病患者（p<0.01）。CD4+CD25+细胞的 SI 与二聚体 IgA 产生细胞的 SI 呈负相关。
结果表明，扁桃体中的 CD4+CD25+细胞和二聚体 IgA 产生细胞可能与 IgAN 的发病机制有关。
