Natural Killer Cells Are Characterized by the Concomitantly Increased Interferon-γ and Cytotoxicity in Acute Resolved Hepatitis B Patients
Open Access
- 1 November 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (11), e49135
- https://doi.org/10.1371/journal.pone.0049135
Abstract
Natural killer (NK) cells are abundant in the liver and have been implicated in inducing hepatocellular damage in patients with chronic hepatitis B virus (HBV) infection. However, the role of NK cells in acute HBV infection remains to be elucidated. We comprehensively characterized NK cells and investigated their roles in HBV clearance and liver pathology in 19 chronic hepatitis B (CHB) patients and 21 acute hepatitis B (AHB) patients as well as 16 healthy subjects. It was found that NKp46+ NK cells were enriched in the livers of AHB and CHB patients. We further found that peripheral NK cells from AHB patients expressed higher levels of activation receptors and lower levels of inhibitory receptors than those from CHB patients and HC subjects, thus displaying the increased cytolytic activity and interferon-γ production. NK cell activation levels were also correlated positively with serum alanine aminotransferase levels and negatively with plasma HBV DNA levels in AHB patients, which is further confirmed by the longitudinal follow-up of AHB patients. Serum pro-inflammatory cytokine and chemokine levels were also increased in AHB patients as compared with CHB and HC subjects. Thus, the concomitantly increased interferon-γ and cytotoxicity of NK cells were associated with liver injury and viral clearance in AHB patients.Keywords
This publication has 37 references indexed in Scilit:
- Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus InfectionsJournal of Virology, 2009
- Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patientsClinical Immunology, 2008
- Intrahepatic Expression of Genes Affiliated with Innate and Adaptive Immune Responses Immediately after Invasion and during Acute Infection with Woodchuck HepadnavirusJournal of Virology, 2008
- Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infectionThe Journal of Experimental Medicine, 2008
- Aberrant Lymphocyte Activation Precedes Delayed Virus-Specific T-Cell Response after both Primary Infection and Secondary Exposure to Hepadnavirus in the Woodchuck Model of Hepatitis B Virus InfectionJournal of Virology, 2008
- Dynamic Programmed Death 1 Expression by Virus-Specific CD8 T Cells Correlates With the Outcome of Acute Hepatitis BGastroenterology, 2008
- Bim-mediated deletion of antigen-specific CD8+ T cells in patients unable to control HBV infectionJCI Insight, 2008
- Functions of natural killer cellsNature Immunology, 2008
- The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infectionHepatology, 2007
- Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV InfectionJournal of Virology, 2007