Natural Killer Cells Are Characterized by the Concomitantly Increased Interferon-γ and Cytotoxicity in Acute Resolved Hepatitis B Patients

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 inve...

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Published in:PloS one Vol. 7; no. 11; p. e49135
Main Authors: Zhao, Juanjuan, Li, Yonggang, Jin, Lei, Zhang, Shuye, Fan, Rong, Sun, Yanling, Zhou, Chunbao, Shang, Qinghua, Li, Wengang, Zhang, Zheng, Wang, Fu-Sheng
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.11.2012
Public Library of Science (PLoS)
Subjects:
Acute Disease
Adolescent
Adult
Aged
Alanine
Alanine transaminase
Biophysics
CD56 Antigen - biosynthesis
Cell activation
Chronic infection
Cytokines
Cytolytic activity
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA, Viral - genetics
Female
Flow Cytometry
Gastroenterology
Hepatitis
Hepatitis B
Hepatitis B - blood
Hepatitis B - therapy
Hepatitis B virus
Hepatitis B, Chronic - blood
Hepatitis B, Chronic - therapy
Hepatology
Humans
Immunohistochemistry - methods
Immunotherapy
Infections
Inflammation
Interferon
Interferon-gamma - metabolism
Killer Cells, Natural - cytology
Liver
Liver - pathology
Lymphocytes
Male
Medicine
Middle Aged
Natural killer cells
Pathogenesis
Patients
Receptors
T cell receptors
Toxicity
Viruses
Beijing China
China
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary: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.
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Conceived and designed the experiments: JJZ ZZ YGL F-SW. Performed the experiments: JJZ YGL LJ SYZ RF YLS CBZ. Analyzed the data: JJZ ZZ CBZ SYZ. Contributed reagents/materials/analysis tools: JJZ CBZ QHS. Wrote the paper: JJZ ZZ F-SW. Enrolled patients: YGL JL RF YLS QHS WGL. Sampled: YGL JL RF YLS QHS.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0049135