Tordjmann T, Soulie A, Guettier C, Schmidt M, Berthou C, Beaugrand M, Sasportes M
Service d'Hépato-Gastroentérologie, Hôpital Jean Verdier, Bondy, France.
Liver. 1998 Dec;18(6):391-7. doi: 10.1111/j.1600-0676.1998.tb00823.x.
Cytotoxic T lymphocytes and Kupffer cells are essential components of the immune response during liver diseases. Recent studies have highlighted the role of cytotoxic T lymphocytes using Fas and its ligand in induced hepatocyte death during acute and chronic hepatitis.
In the present work, the main purpose was to investigate perforin and granzyme B expression in liver biopsies of patients with chronic hepatitis (10 HBV, 14 HCV and 10 autoimmune hepatitis) using immunohistochemistry. The liver biopsies of two normal individuals were also studied in the same conditions.
Few intrahepatic T lymphocytes expressed perforin and granzyme B, while a large number of Kupffer cells were positive for both proteins in all the patients tested. The co-localization of perforin and granzyme B, and CD3 or CD68 antigens was visualized, respectively, in T cells and Kupffer cells, using confocal microscopy. In situ hybridization assays confirmed that perforin and granzyme B mRNAs were present in the liver during chronic hepatitis. The results were similar among the three groups of patients and whatever the activity of the disease. Perforin and granzyme B expression was lacking in liver samples from normal individuals.
These data suggest a minor role for the T cell-mediated perforin/granzyme B death pathway, and a putative role for Kuppfer cells via lytic protein release, during chronic hepatitis.
细胞毒性T淋巴细胞和库普弗细胞是肝脏疾病免疫反应的重要组成部分。最近的研究强调了细胞毒性T淋巴细胞利用Fas及其配体在急性和慢性肝炎诱导肝细胞死亡中的作用。
在本研究中，主要目的是使用免疫组织化学研究慢性肝炎患者（10例乙肝、14例丙肝和10例自身免疫性肝炎）肝活检组织中穿孔素和颗粒酶B的表达。同时在相同条件下研究了两名正常个体的肝活检组织。
在所有检测患者中，肝内很少有T淋巴细胞表达穿孔素和颗粒酶B，而大量库普弗细胞这两种蛋白均呈阳性。使用共聚焦显微镜分别在T细胞和库普弗细胞中观察到穿孔素和颗粒酶B与CD3或CD68抗原的共定位。原位杂交分析证实慢性肝炎期间肝脏中存在穿孔素和颗粒酶B的mRNA。三组患者之间以及无论疾病活动程度如何，结果均相似。正常个体的肝脏样本中缺乏穿孔素和颗粒酶B的表达。
这些数据表明在慢性肝炎期间，T细胞介导的穿孔素/颗粒酶B死亡途径作用较小，而库普弗细胞通过释放溶解蛋白可能发挥作用。
