Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells
Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells
复制标题
DOI：
10.1002/hep.24807
复制
发表时间：
2012-04-01
期刊：
影响因子：
13.5
通讯作者：
Mack, Cara L.
中科院分区：
文献类型：
--
作者：
Brindley, Stephen M.;Lanham, Allison M.;Mack, Cara L.
胆道闭锁(BA)是一种进行性炎症性胆管疾病，最终导致肝外和肝内胆管纤维化。关于BA发病机制的一个主要理论是，胆管损伤是由病毒感染引发的，随后是胆管靶向的自身免疫反应。自身免疫的一种机制是调节性T细胞(Tregs)数量或功能减少。这项研究的目的是从诊断为BA的婴儿身上识别潜在的病毒特异性肝T细胞，以证实该病毒与早期胆管损伤有关。一个次目标是确定病毒感染的存在是否与Tregs的数量变化有关。来自BA和对照组的肝T细胞在含有多种病毒或对照蛋白的情况下与抗原提呈细胞共同培养。56%的BA患者对巨细胞病毒(CMV)的反应中产生干扰素-γ的肝脏T细胞显著增加，而对其他病毒或对照组CMV的反应最小。此外，BA血浆CMV免疫球蛋白M(IgM)与肝脏T细胞CMV反应性呈正相关。对外周血Tregs的研究发现，与对照组相比，BA患者的Treg频率显著降低，其中CMV阳性的BA患者的Treg频率显著降低。结论：大多数BA患者确诊时肝脏T细胞对CMV有反应，提示围产期CMV感染可能是胆管损伤的始动因素。BA中Tregs的缺乏意味着炎症和自身反应性的抑制降低，有可能导致胆管损伤的加重。(2012国际肝病)
Biliary atresia (BA) is a progressive, inflammatory cholangiopathy that culminates in fibrosis of extrahepatic and intrahepatic bile ducts. A leading theory on the pathogenesis of BA is that the bile duct damage is initiated by a virus infection, followed by a bile duct-targeted autoimmune response. One mechanism of autoimmunity entails a diminished number or function of regulatory T cells (Tregs). The aim of this study was to identify potential virus-specific liver T cells from infants with BA at the time of diagnosis, implicating the virus involved in early bile duct damage. A subaim was to determine if the presence of virus infection was associated with quantitative changes in Tregs. Liver T cells from BA and control patients were cultured with antigen-presenting cells in the presence of a variety of viral or control proteins. 56% of BA patients had significant increases in interferon-gamma-producing liver T cells in response to cytomegalovirus (CMV), compared with minimal BA responses to other viruses or the control group CMV response. In addition, a positive correlation between BA plasma CMV immunoglobulin M (IgM) and liver T-cell CMV reactivity was identified. Investigation of peripheral blood Tregs revealed significant deficits in Treg frequencies in BA compared with controls, with marked deficits in those BA patients who were positive for CMV. Conclusion: Liver T-cell responses to CMV were identified in the majority of BA patients at diagnosis, suggesting perinatal CMV infection as a plausible initiator of bile duct damage. Deficiency of Tregs in BA implies decreased inhibition of inflammation and autoreactivity, potentially allowing for exaggerated bile duct injury. (HEPATOLOGY 2012)