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Front. Immunol. | doi: 10.3389/fimmu.2019.02240

Heterogeneity of HBV-specific CD8+ T-cell failure: implications for immunotherapy

Kathrin Heim1, 2, Christoph Neumann-Haefelin1,  Robert Thimme1 and  Maike Hofmann1*
  • 1Department of Medicine II Gastroenterology, Hepatology, Endocrinology and Infectious Disease, Freiburg University Medical Center, Germany
  • 2Faculty of Biology, University of Freiburg, Germany

Chronic hepatitis B virus (HBV) infection is a major global health burden affecting around 257 million people worldwide. The consequences of chronic HBV infection include progressive liver damage, liver cirrhosis and hepatocellular carcinoma. Although current direct antiviral therapies successfully lead to suppression of viral replication and deceleration of liver cirrhosis progression, these treatments are rarely curative and patients often require a life-long therapy. Based on the ability of the immune system to control HBV infection in at least a subset of patients, immunotherapeutic approaches are promising treatment options to achieve HBV cure. In particular, T cell-based therapies are of special interest since CD8+ T cells are not only capable to control HBV infection but also to eliminate HBV-infected cells. However, recent data show that the molecular mechanisms underlying CD8+ T-cell failure in chronic HBV infection depend on the targeted antigen and thus different strategies to improve the HBV-specific CD8+ T-cell response are required. Here, we review the current knowledge about the heterogeneity of impaired HBV-specific T-cell populations and the potential consequences for T cell-based immunotherapeutic approaches in HBV cure.

Keywords: Chronic HBV infection, CD8+ T cells, exhaustion, T-cell heterogeneity, Viral antigen

Received: 22 Jul 2019; Accepted: 04 Sep 2019.

Copyright: © 2019 Heim, Neumann-Haefelin, Thimme and Hofmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Maike Hofmann, Department of Medicine II Gastroenterology, Hepatology, Endocrinology and Infectious Disease, Freiburg University Medical Center, Freiburg, 79106, Germany,