Karimi Mohammad Hossein, Shariat Afsoon, Yaghobi Ramin, Mokhtariazad Talat, Moazzeni Seyed Mohammad
Mohammad Hossein Karimi, Ramin Yaghobi, Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran.
World J Transplant. 2016 Jun 24;6(2):336-46. doi: 10.5500/wjt.v6.i2.336.
To study the impact of association between cytomegalovirus (CMV) pathogenesis with dendritic cell (DC) maturation and function was evaluated in CMV reactivated liver transplanted patients in comparing with non-reactivated ones, and healthy controls.
Monocyte derived dendritic cells (MoDCs) was generated from collected ethylenediaminetetraacetic acid-treated blood samples from patient groups and controls. In these groups, expression rates and mean fluorescent intensity of DC markers were evaluated using flowcytometry technique. Secretion of cytokines including: interleukin (IL)-6, IL-12 and IL-23 were determined using enzyme-linked immunosorbent assay methods. The gene expression of toll-like receptor 2 (TLR2), TLR4 and IL-23 were analyzed using in-house real-time polymerase chain reaction protocols.
Results have been shown significant decreases in: Expression rates of MoDC markers including CD83, CD1a and human leukocyte antigen DR (HLA-DR), the mean fluorescence intensitys for CD1a and HLA-DR, and secretion of IL-12 in CMV reactivated compared with non-reactivated liver transplanted patients. On the other hand, significant increases have been shown in the secretions of IL-6 and IL-23 and gene expression levels of TLR2, TLR4 and IL-23 from MoDCs in CMV reactivated compared with non-reactivated liver transplanted recipients.
DC functional defects in CMV reactivated recipients, such as decrease in expression of DC maturation markers, increase in secretion of proinflammatory cytokines, and TLRs can emphasize on the importance of CMV infectivity in development of liver rejection in transplanted patients.
通过比较巨细胞病毒(CMV)再激活的肝移植患者与未再激活的患者以及健康对照,研究CMV发病机制与树突状细胞(DC)成熟及功能之间关联的影响。
从患者组和对照组采集的经乙二胺四乙酸处理的血样中生成单核细胞衍生的树突状细胞(MoDCs)。在这些组中,使用流式细胞术技术评估DC标志物的表达率和平均荧光强度。使用酶联免疫吸附测定法测定包括白细胞介素(IL)-6、IL-12和IL-23在内的细胞因子的分泌。使用内部实时聚合酶链反应方案分析Toll样受体2(TLR2)、TLR4和IL-23的基因表达。
结果显示,与未再激活的肝移植患者相比,CMV再激活患者中MoDC标志物包括CD83、CD1a和人类白细胞抗原DR(HLA-DR)的表达率、CD1a和HLA-DR的平均荧光强度以及IL-12的分泌均显著降低。另一方面,与未再激活的肝移植受者相比,CMV再激活患者中MoDCs分泌的IL-6和IL-23以及TLR2、TLR4和IL-23的基因表达水平显著增加。
CMV再激活受者中的DC功能缺陷,如DC成熟标志物表达降低、促炎细胞因子分泌增加以及Toll样受体,可强调CMV感染性在移植患者肝排斥反应发生中的重要性。