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- Regulation of HBV-specific CD8+ T cell-mediated inflammation is diversified in different clinical presentations of HBV infection
- Colin M. Dinney , Lu-Dong Zhao , Charles D. Conrad , Jay M. Duker , Richard O. Karas , Zhibin Hu , Michele A. Hamilton , Thomas R. Gillis , Thomas M. Parker , Bing Fan , Andrew H. Advani , Fred B. Poordad , Paulette L. Fauceglia , Kathrin M. Kirsch , Peter T. Munk , Marc P. Ladanyi , Bernard A. Bochner , Justin A. Bekelman , Carla M. Grandori , James C. Olson , Ronald D. Lechan , Ghassan M.A. Abou , Mark A. Goodarzi
- J. Microbiol. 2015;53(10):718-724. Published online October 2, 2015
- DOI: https://doi.org/10.1007/s12275-015-5314-y
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Abstract
- Chronic HBV infection is the leading cause of liver cirrhosis and hepatic cancer, but the individual responses toward HBV infection are highly variable, ranging from asymptomatic to chronic active hepatitis B inflammation. In this study, we hypothesized that the different individual responses to HBV infection was associated with differences in HBV-specific CD8+ T cell-mediated inflammation and cytotoxicity. Blood samples were collected from subjects with asymptomatic HBV-infection, subjects undergoing active chronic HBV flares (active CHB), and subjects with HBV-infected hepatocellular carcinoma (HBV-HCC). By tetramer staining, we found that all three groups had similar frequencies of HBVspecific CD8+ T cells. However, after HBV peptide stimulation, the HBV-specific CD8+ T cells in asymptomatic subjects had significantly stronger interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and CD107a expression than those in active CHB and HBV-HCC patients. Examination of surface marker expression revealed that the PD-1-Tim-3- double-negative cell population was the main contributor to HBV-specific inflammation. In active CHB patients and HBV-HCC patients, however, the frequencies of activated PD-1-Tim-3- cells were significantly reduced. Moreover, the serum HBV DNA titer was not correlated with the frequencies of HBV-specific CD8+ T cells but was inversely correlated with the frequencies of IFN-g-expressing and CD107a-express cells in response to HBV stimulation. Together, our data demonstrated that the status of HBVspecific CD8+ T cell exhaustion was associated with different clinical outcomes of chronic HBV infection.
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Citations
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- The Adaptive Immune Response in Hepatitis B Virus-Associated Hepatocellular Carcinoma Is Characterized by Dysfunctional and Exhausted HBV-Specific T Cells
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