肝或肾移植术后纤维化胆汁淤积性肝炎肝组织中CD4^＋CD25^＋调节性T淋巴细胞的表达

Detection of CD4^＋CD25^＋ regulatory T cells in liver tissues of fibrosing cholestatic hepatitis after liver and kidney transplantation

目的观察肝或肾移植术后纤维化胆汁淤积性肝炎（FCH）患者肝组织中CD4^＋CD25^＋调节性T淋巴细胞的表达及分布,并对其作用机制进行初步探讨。方法对5例FCH患者进行肝活体组织病理学检查;采用免疫组织化学法检测肝组织中CD4^＋CD25^＋调节性T淋巴细胞的特异性标记物叉状头/翅膀状螺旋回转录因子（FOXP3）;采用末端脱氧核苷酸转移酶介导的脱氧三磷酸尿苷缺口末端标记（TUNEL）检测试剂盒对肝组织内的肝细胞凋亡情况进行观察。结果5例FCH患者中,3例为原位肝移植患者,2例为肾移植患者。光学显微镜下,肝脏汇管区及汇管区周围出现纤维化,肝细胞及胆小管明显胆汁淤积,肝细胞气球样变及毛玻璃样变。免疫组织化学检测显示HBsAg、HBcAg及前S1抗原阳性。FOXP3阳性信号定位于淋巴细胞胞质内,阳性细胞主要聚集在汇管区,小叶肝窦内可见散在的单个淋巴细胞呈阳性表达。汇管区周围可见较多的凋亡细胞。正常肝组织HBsAg、HBcAg及前S1抗原均为阴性,汇管区内有少量的阳性CD4^＋CD25^＋调节性T淋巴细胞,小叶内偶见凋亡细胞。结论FCH具有独特的组织学特征,可能与肝组织中的FOXP3高表达有关。

Objectives To study the expression and distribution of CD4^＋CD25^＋ regulatory T cells （Treg） in liver tissues of patients with fibrosing cholestatic hepatitis （FCH） after liver and kidney transplanta- tion and to investigate their roles in the pathogenesis of FCH. Methods Liver biopsy specimens from five patients with FCH were studied histopathologically. A specific marker for CD4^＋CD25^＋ regulatory T cells in those specimens was detected with anti-FOXP3 monoclonal antibody by immunohistochemistry. Apoptoses of hepatocytes were detected with in situ apoptosis detection TUNEL kit. Results Fibrosis in portal and around portal areas, cholestasis in some of the hepatocytes and canaliculi, widespread ballooning and groundglass appearance of liver cells, and positivity of HBsAg and HBcAg and Pre-S 1 protein were seen in the livers of all cases. The positive signal of FOXP3 was located in the cytoplasm of lymphocytes and the positive cells were mainly aggregated in the portal areas as well as occasionally appearing in the hepatic sinusoids. There were many more apoptotic hepatocytes near the portal areas. Conclusions Fibrosing cholestatic hepatitis has specific pathological characteristics which might be caused by high expressions of FOXP3 in liver tissues.