- Regulation of HBV-specific CD8+ T cell-mediated inflammation is diversified in different clinical presentations of HBV infection
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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
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J. Microbiol. 2015;53(10):718-724. Published online October 2, 2015
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DOI: https://doi.org/10.1007/s12275-015-5314-y
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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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