Research group - N. Semmo

Hepatitis B and C

Semmo Nasser, Principal Investigator
Mirjam Kolev, MD
Stefan Diem, MD

T- cell Immunology of viral Hepatitis (B and C)

Virus-specific T Cell Responses in Viral Hepatitis

Worldwide, about 170 million people are infected with Hepatitis C virus (HCV). There is considerable evidence that T cell responses play an important role in the outcome of HBV and HCV infection, e.g. viral elimination versus persistence.
Viral persistence is due to multiple mechanisms leading to the failure of the virus-specific T cell responses. These mechanisms include primary T cell failure, T cell exhaustion, viral escape mutants, as well as T cell dysfunction. Once viral persistence has been established, HBV or HCV infection can progress to liver fibrosis and cirrhosis with an enhanced risk for HCC.
The focus of our group is the identification and characterization of virus-specific CD4+ T cell responses during acute and chronic HBV and HCV infection. Several groups have demonstrated that during chronic HCV infection, HCV-specific CD4+ T cell responses are weak or absent. However, the functional status of HCV-specific CD4+ T cells in persistent infection is poorly understood and it may be necessary to use various techniques for their detection.
In the last years, using HCV proteins and overlapping peptides, we have been able to identify HCV-specific CD154+CD4+ T cells in chronic HCV infection that are enriched in the liver. These cells do not produce IFN-γ and IL-2 and do not have the ability to proliferate (IFN-γ/IL-2/proliferation), suggesting that HCV-specific CD4+ T cells do exist, but lack function.

Figure 1: HCV-specific CD154+CD4+ T cells in chronic HCV infection
To what extent such cells play a role in determining disease outcome in HCV as well as in HBV, and whether they can be modulated to prevent disease progression remain important questions, which we will attempt to address in our group.


Research Focus

T cell dysfunction
T cell exhaustion
Viral clearance prediction
CD154/CD40 ligand expression

Research ratios

Humans : Animals

24 : 1

Top Major MeSH Headings

CD4+ T lymphocytes
Hepatitis C
IFNγ/cytokine production
Differential diagnosis
Liver Transplantation
T lymphocyte epitopes
Cellular Immunity