Natural killer (NK) cells play a major role in anti-viral immunity as first line defense and regulation of virus-specific T cell responses. OBJECTIVE: To investigate phenotype and function of NK cells in patients with chronic hepatitis B virus (HBV) infection and the effect of anti-viral therapy. METHODS: Peripheral blood NK cells from 40 chronic HBV patients were compared toNK cells of 25 healthy controls. The effect of entecavirinduced viral load reduction on NK cell phenotype and function were investigated in 15 chronic HBV patients. RESULTS: NK cell numbers and subset distribution did not differ. Concerning their function, the cytotoxic capacity was retained, whereas NK cell activation and subsequent IFNy and TN Fa production, especially of the CD56dlm subset. were strongly hampered in chronic HBV. This functional dichotomy was paralleled by an altered activation state, elevated expression of NKG2A and downregulated expression of CD16 and NKp30, which correlated with serum HBV-DNA load. Anti-viral therapy partially restored NK cell phenotype, as shown by NKG2A downregulation. Moreover, viral replication inhibition improved IFNy production as a result of an increased ability of CD56dlm NK cells to become activated de novo. This improved NK cell activation and function correlated with therapy-induced reduction in serum ALT levels, but not HBV-DNA load. coNCLUSIONS: The specific defect in CD56dim NK cell activation and the reduced capacity to produce anti-viral and Th 1-skewing cytokines may play a role in HBV persistence. Restoration of this NK cell cytokine producing capacity as achieved by viral load reduction could therefore contribute to definite clearance of the virus.

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Keywords Hepatitis B, virology, infectious diseases, chronic hepatitis B, DNA
Promotor H.L.A. Janssen (Harry)
Publisher Erasmus University Rotterdam
Sponsor The studies described in this thesis were financially supported by a personal grant provided by the Board of the Erasmus University Rotterdam (ref. NWO-Mozaiek). the Foundation for Liver and Gastrointestinal Research (SLO) Rotterdam. and partially supported by unrestricted educational grants by Bristol-Myers Squibb and Gilead Sciences. Financial support for printing this thesis was kindly provided by the department of Gastroenterology and Hepatology, Erasmus Medical Centre University Hospital and the Erasmus University Rotterdam. The Netherlands.
ISBN 978-90-90-26958-0
Persistent URL hdl.handle.net/1765/50200
Tjwa, E.T.T.L. (2012, September 5). Natural killer cells in chronic hepatitis B. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/50200