Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea.
Am J Nephrol. 2012;35(2):164-74. doi: 10.1159/000334928. Epub 2012 Jan 25.
BACKGROUND/AIMS: Recent evidence has shown that an inflammatory process is involved in the development and progression of diabetic nephropathy. This study examined the impact of activated intrarenal lymphocytes in this inflammatory process.
We studied T cell recruitment in mice with streptozotocin (STZ)-induced diabetes by flow cytometry and immunohistochemistry. The kidney biopsy specimens from patients with type 2 diabetes mellitus and diabetic nephropathy were evaluated by immunohistochemistry.
In flow cytometry, intrarenal CD3+ T cells were significantly increased in proteinuric mice at 20 weeks after STZ injection. However, the population of T cells and B cells in diabetic spleen was not different from that of control mice. Immunohistochemistry also showed a marked infiltration of interstitial CD4+, CD8+ T cells in diabetic kidney. Interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) mRNA expression was significantly increased in diabetic mouse kidney compared with controls. Interestingly, flow cytometry analysis of kidney-derived mononuclear cells from diabetic mice showed significantly increased production of IFN-γ and TNF-α by CD3+ T cells. Type 2 diabetic patients also showed a marked increase in CD4+, CD8+ and CD20+ cells in interstitium, and the number of CD4+ and CD20+ cells correlated with the amount of proteinuria.
Our results clearly showed that aberrant intrarenal infiltration and the activation of T cells in interstitium are the underlying immunopathological mechanisms of diabetic kidney injury.
背景/目的：最近的证据表明，炎症过程参与了糖尿病肾病的发生和发展。本研究探讨了激活的肾内淋巴细胞在这一炎症过程中的影响。
我们通过流式细胞术和免疫组织化学研究了链脲佐菌素（STZ）诱导的糖尿病小鼠中 T 细胞的募集。通过免疫组织化学评估了 2 型糖尿病和糖尿病肾病患者的肾活检标本。
在流式细胞术中，STZ 注射后 20 周时，蛋白尿小鼠的肾内 CD3+T 细胞明显增加。然而，糖尿病脾中的 T 细胞和 B 细胞的数量与对照小鼠无差异。免疫组织化学也显示出糖尿病肾脏间质中 CD4+、CD8+T 细胞的明显浸润。与对照组相比，糖尿病小鼠肾脏中的干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）mRNA 表达显著增加。有趣的是，糖尿病小鼠肾源性单核细胞的流式细胞术分析显示 CD3+T 细胞产生 IFN-γ和 TNF-α的显著增加。2 型糖尿病患者的间质中也明显增加了 CD4+、CD8+和 CD20+细胞，CD4+和 CD20+细胞的数量与蛋白尿的量相关。
我们的研究结果清楚地表明，异常的肾内浸润和间质中 T 细胞的激活是糖尿病肾损伤的潜在免疫病理机制。
