研究文章Viral load reduction improves activation and function of natural kil

StephenW

一个研究文章
J Hepatol. 2010 Sep 6. [Epub ahead of print]

Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B.

Tjwa ET, van Oord GW, Hegmans JP, Janssen HL, Woltman AM.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.


Abstract

BACKGROUND& AIMS: Natural killer (NK) cells play a major role in anti-viralimmunity as first line defense and regulation of virus-specific T cellresponses. This study aimed to investigate phenotype and function of NKcells in patients with chronic hepatitis B virus (HBV) infection and to study the effect of anti-viral therapy.

METHODSeripheral blood NK cells from 40 chronic HBV patients were compared toNK cells of 25 healthy controls. The effect of entecavir-induced viralload reduction on NK cell phenotype and function was investigated in 15chronic HBV patients.

RESULTS: NK cell numbers and subsetdistribution did not differ between HBV patients and normal subjects.In chronic HBV patients, the cytotoxic capacity was retained, but NKcell activation and subsequent IFNγ, and TNFα production, especially ofthe CD56(dim) subset, were strongly hampered. This functional dichotomywas paralleled by an altered activation state, elevated expression ofNKG2A, and downregulated expression of CD16 and NKp30, which correlatedwith serum HBV-DNA load. Anti-viral therapy partially restored NK cellphenotype, as shown by NKG2A downregulation. Moreover, viral replicationinhibition improved IFNγ production as a result of an increased abilityof CD56(dim) NK cells to become activated de novo. This improved NKcell activation and function which correlated with therapy-inducedreduction in serum ALT levels, but not HBV-DNA load.

CONCLUSIONS:The specific defect in CD56(dim) NK cell activation and the reducedcapacity to produce anti-viral and Th1-skewing cytokines may play arole in HBV persistence. Restoration of this NK cell cytokine-producingcapacity as achieved by viral load reduction could therefore contributeto definite clearance of the virus.

Copyright © 2010 EuropeanAssociation for the Study of the Liver. Published by Elsevier B.V. Allrights reserved.                        




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