Tang T J, Kwekkeboom J, Laman J D, Niesters H G M, Zondervan P E, de Man R A, Schalm S W, Janssen H L A
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, the Netherlands.
J Viral Hepat. 2003 May;10(3):159-67. doi: 10.1046/j.1365-2893.2003.00412.x.
Cytotoxic T lymphocytes (CTL) and Kupffer cells play an important role in the immune control of hepatitis B virus (HBV), but may also induce liver injury during infection. We investigated the intrahepatic immune response in liver biopsies of chronic HBV patients in relation to inflammatory liver injury and viral control. Forty-seven liver biopsies from patients with chronic HBV with varying degrees of inflammation (ALT values) were selected. Acute hepatitis and normal liver specimens served as controls. Immune effector cells, cytotoxic effector molecules and cytokine producing cells were quantified after immunohistochemical staining in lobular and portal areas of the biopsies. The intralobular number of CD8+ T-lymphocytes was significantly decreased in biopsies of patients with high ALT (r = -0.54; P < 0.001). Higher ALT-values were correlated with increased numbers of granzyme+ cells in portal areas (r = 0.65; P < 0.001) and higher numbers of intralobular Fas-L+ cells (r = 0.32; P = 0.05). Fas-L was expressed on Kupffer and lymphoid cells. More intralobular CD8+ T-lymphocytes were found in HBeAg- than in HBeAg+ patients (P = 0.002). But IFN-gamma and TNF-alpha producing cells were observed sporadically in chronic HBV patients. Hence, in chronic HBV infection, low viral replication and HBeAg negativity is related to increased presence of intralobular CD8+ T-lymphocytes. Persistence of the virus may be caused by the absence of cells producing anti-viral cytokines in the liver. Inflammatory liver injury during chronic HBV infection is probably not the result of increased numbers of infiltrating CD8+ T-lymphocytes, but of Fas-L expression by Kupffer cells and increased cytolytic activity of cells in portal areas.
细胞毒性T淋巴细胞（CTL）和库普弗细胞在乙型肝炎病毒（HBV）的免疫控制中发挥重要作用，但在感染过程中也可能导致肝损伤。我们研究了慢性HBV患者肝活检中的肝内免疫反应与炎症性肝损伤和病毒控制的关系。选取了47例患有不同程度炎症（ALT值）的慢性HBV患者的肝活检样本。急性肝炎和正常肝脏标本作为对照。在活检样本的小叶和门管区进行免疫组织化学染色后，对免疫效应细胞、细胞毒性效应分子和细胞因子产生细胞进行定量分析。ALT水平高的患者活检样本中，小叶内CD8 + T淋巴细胞数量显著减少（r = -0.54；P < 0.001）。较高的ALT值与门管区颗粒酶 + 细胞数量增加（r = 0.65；P < 0.001）和小叶内Fas-L + 细胞数量增加相关（r = 0.32；P = 0.05）。Fas-L在库普弗细胞和淋巴细胞上表达。HBeAg阴性患者的小叶内CD8 + T淋巴细胞比HBeAg阳性患者更多（P = 0.002）。但在慢性HBV患者中，偶尔观察到产生IFN-γ和TNF-α的细胞。因此，在慢性HBV感染中，低病毒复制和HBeAg阴性与小叶内CD8 + T淋巴细胞数量增加有关。病毒持续存在可能是由于肝脏中缺乏产生抗病毒细胞因子的细胞。慢性HBV感染期间的炎症性肝损伤可能不是浸润性CD8 + T淋巴细胞数量增加的结果，而是库普弗细胞Fas-L表达和门管区细胞溶细胞活性增加的结果。
