CD8+ T cell memory in chronic viral hepatitis

Viral hepatitis caused by infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) can be either acute or chronic and represents a major global health burden. CD8+ T cells are major
determinants for the outcome. Chronic viral hepatitis is characterized by a weak, negatively regulated virus-specific CD8+ T cell response in association with persisting antigen stimulation frequently called T cell exhaustion. By using the unique model of cure of chronic HCV infection by direct acting antivirals (DAA) we showed that an HCV-specific memory-like CD8+ T cells response is established following antigen withdrawal. Memory-like HCV-specific CD8+ T cells are phenotypically, functionally and transcriptionally different to classical memory CD8+ T cells by maintaining a molecular scar of chronicity after DAA-mediated HCV cure. A chronic scar can also be observed in HBV-specific CD8+ T cells after HBV cure indicating that scarring is potentially a general mechanism associated with persisting antigen stimulation in chronic infections.

Dr. Maike Hofmann is trained in Molecular Medicine with focus in immunology and virology, I am interested in translational questions concerning the cytotoxic cellular immune response in viral infections and cancer. My experimental experience covers analysis of T cells and NK cells in mouse models as well as in patient samples by state-of-the-art immunological assays and cutting-edge single cell technologies. A main focus of my work in the last years relates to mechanisms underlying the T cell and NK cell dysfunction in the context of chronic viral hepatitis caused by hepatitis B and C viruses (HBV and HCV) and in liver cancer with the aim to provide rationales for the identification of biomarkers and potential immunotherapeutic approaches that can also be applied to other chronic diseases. In addition, I am interested in understanding shared and diverging principles of T cell and NK cell memory in chronic versus self-limiting viral infections with HBV, HCV, Influenza A virus, cytomegalovirus (CMV) , Epstein-Barr virus (EBV) and most recently SARS-CoV-2 and mRNA vaccination. Currently, I am group leader and spokesperson of the research unit in the Department of Medicine II, University Medical Center, Freiburg, Germany.