Laboratory of Immunology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brasil.
Ann Diagn Pathol. 2013 Feb;17(1):75-9. doi: 10.1016/j.anndiagpath.2012.08.002. Epub 2012 Sep 8.
The kidney transplant is the main therapeutic alternative for end-stage kidney disease, and rejection is a major complication. The expression of proinflammatory cytokines is related to graft loss, whereas anti-inflammatory cytokines are associated with graft protection. The objective of this study is to evaluate the "in situ" expression of cytokines T helper 1 (tumor necrosis factor α [TNF-α]), T helper 17 (interleukin 17 [IL-17]), and regulatory T cell (transforming growth factor β [TGF-β]) and the expression of forkhead box P3 (FoxP3) in allograft kidney. We evaluated in situ expression of cytokines in allograft kidney under rejection process by indirect immunohistochemistry. Eighteen renal graft biopsies were from patients with episodes of rejection. The in situ expression of IL-17, TNF-α, and TGF-β was significantly higher in patients with acute rejection when compared with the control group. In contrast, analysis of FoxP3 expression showed few positive cells in patients with acute rejection compared with the control group. The results suggest that the expression of proinflammatory cytokines (IL-17 and TNF-α) contributes to the mechanisms of kidney transplant rejection. The increase in TGF-β expression might be an attempt to establish a process of immunoregulation or even to induce higher production of IL-17. The last hypothesis is supported by the observation of a reduced expression of FoxP3 and elevated levels of IL-17.
肾移植是治疗终末期肾病的主要治疗方法,而排斥反应是主要并发症。促炎细胞因子的表达与移植物丢失有关,而抗炎细胞因子与移植物保护有关。本研究的目的是评估细胞因子辅助性 T 细胞 1(肿瘤坏死因子 α [TNF-α])、辅助性 T 细胞 17(白细胞介素 17 [IL-17])和调节性 T 细胞(转化生长因子 β [TGF-β])的“原位”表达,以及同种异体肾中的叉头框 P3(FoxP3)的表达。我们通过间接免疫组织化学评估排斥过程中同种异体肾中的细胞因子原位表达。18 例肾移植活检来自发生排斥反应的患者。与对照组相比,急性排斥反应患者的 IL-17、TNF-α 和 TGF-β 的原位表达明显升高。相比之下,FoxP3 表达分析显示,急性排斥反应患者的阳性细胞数与对照组相比较少。结果表明,促炎细胞因子(IL-17 和 TNF-α)的表达有助于肾移植排斥反应的机制。TGF-β 表达的增加可能是建立免疫调节过程的尝试,甚至可能诱导更高水平的 IL-17 产生。FoxP3 表达减少和 IL-17 水平升高的观察结果支持最后一种假设。