乙型肝炎病毒特异性细胞毒性T细胞在肝脏损伤和病毒控制中的作用

Role of hepatitis B virus specific cytotoxic T cells in liver damage and viral control

摘要
为了了解细胞毒性T细胞在肝脏损伤和病毒控制中的作用，我们使用了人类组织相容性白细胞抗原(HLA)-HLA肽四聚体，允许对循环和肝浸润的HBV特异性CD8细胞进行体外直接定量。

研究在两组患者中进行，一组无肝炎症，乙肝病毒复制量最小，另一组肝损伤、炎症，病毒复制量高。与预期相反，前一组肝内HBV特异性CD8细胞高频率出现，缺乏肝脏的免疫病理。在复制中的病毒血症组，病毒特异性T细胞在肝浸润中被稀释;虽然存在大量的细胞浸润，但绝对数量是相似的。在低病毒血症组中，循环中存在的CD8+细胞库在特定病毒识别后能够增殖，而在高病毒血症的肝脏炎症患者中则无法检测到这一点。

这些结果表明，抑制病毒复制可以独立于肝损伤，当HBV特异性CD8反应不能控制病毒复制时，它不仅可以直接促进肝脏病理，还可以引起非病毒特异性T细胞的招募。

Role of hepatitis B virus specific cytotoxic T cells in liver damage and viral control

Institute of Hepatology, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK
https://doi.org/10.1016/j.antiviral.2003.08.012

Abstract
To understand the role of cytotoxic T cells in liver damage and viral control, we used human histocompatibility leukocyte antigen (HLA)-peptide tetramers that allow direct ex vivo quantification of circulating and liver-infiltrating HBV-specific CD8 cells. Studies were carried out in two groups of patients, one without liver inflammation and minimal HBV replication and the other with liver damage and inflammation along with a high level of viral replication. Contrary to expectation, a high frequency of intrahepatic HBV-specific CD8 cells was found in the former group, i.e., the absence of hepatic immunopathology. In the replicating viraemic group, the virus specific T cells were diluted among the liver infiltrates; although with the massive cellular infiltration that was present, the absolute number was similar. It was also shown that in the low viraemia group the reservoir of CD8+ cells present in the circulation was able to expand after specific virus recognition and that this was not detectable in highly viraemic patients with liver inflammation.

These results show that inhibition of virus replication can be independent of liver damage and when the HBV-specific CD8 response is unable to control virus replication it may contribute to liver pathology not only directly but by causing recruitment of non-virus specific T cells.

https://www.sciencedirect.com/science/article/pii/S016635420300192