The Role of Virus-Specific Cd8+ Cells in Liver Damage and Viral Control during Persistent Hepatitis B Virus Infection
By M. Maini, C. Boni, Chun Kyon Lee, J. Larrubia, S. Reignat, Graham S. Ogg, A. King, J. Herberg, R. Gilson, A. Alisa and 5 more. Journal of Experimental Medicine, 2000
829 citations recorded by the source corpus.
Hepatitis B virus (HBV) is a noncytopathic virus, and the recognition of infected hepatocytes by HBV-specific CD8 cells has been assumed to be the central mechanism causing both liver damage and virus control. To understand the role of cytotoxic T cells in the pathogenesis of HBV infection, we used functional assays that require T cell expansion in vitro and human histocompatibility leukocyte antigen (HLA)-peptide tetramers that allow direct ex vivo quantification of circulating and liver-infiltrating HBV-specific CD8 cells. Two groups of patients with persistent HBV infection were studied: one without liver inflammation and HBV replication, the other with liver inflammation and a high level of HBV replication. Contrary to expectation, a high frequency of intrahepatic HBV-specific CD8 cells was found in the absence of hepatic immunopathology. In contrast, virus-specific T cells were more diluted among liver infiltrates in viremic patients, but their absolute number was similar because of the massive cellular infiltration. Furthermore, inhibition of HBV replication was associated with the presence of a circulating reservoir of CD8+ cells able to expand after specific virus recognition that was not detectable in highly viremic patients with liver inflammation. These results show that in the presence of an effective HBV-specific CD8 response, inhibition of virus replication can be independent of liver damage. When the HBV-specific CD8 response is unable to control virus replication, it may contribute to liver pathology not only directly but by causing the recruitment of nonvirus-specific T cells.
Subfields: Epidemiology, Immunology
View Paper: https://www.semanticscholar.org/paper/1c19ebb175e0b78c44360daa3ab5a4cecb39f4a7
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Epidemiology
In Immunology
Citations in the corpus
- CD8+ T Cells Mediate Viral Clearance and Disease Pathogenesis during Acute Hepatitis B Virus Infection (2003, background): “Furthermore, HBV-specific T cells are detectable in the livers of chronically infected patients, suggesting that they probably contribute to disease pathogenesis, but for functional and/or quantitative reasons, they are unable to terminate the infection (2, 7, 24 , 30).”