Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitits C virus infections.

BACKGROUND & AIMS: The phenotypic and functional
characteristics of natural killer (NK) cells in
chronic hepatitis B virus (HBV) and hepatitis C virus
(HCV) infections are incompletely defined and largely
controversial. METHODS: We studied NK cell receptor
expression, cytotoxic activity, and cytokine production in
peripheral blood mononuclear cells from 35 patients
with chronic hepatitis C, 22 with chronic hepatitis B, and
30 healthy controls. RESULTS: Patients with chronic
HBV infection had an increased proportion of NKG2C
NK cells with normal inhibitory receptor expression and
a lower proportion of activated NK cells compared with
HCV patients, which was associated with normal or
reduced cytolytic activity and markedly dysfunctional
tumor necrosis factor- and interferon- production.
Patients with chronic HCV infection showed a predominantly
activating phenotype, featuring a decreased
percentage of cells expressing the inhibitory receptor
KIR3DL1 and a concomitant increase in the proportion of
NKG2D NK cells. Expression of the CD69 early activation
antigen on NK cells positively correlated with serum
alanine aminotransferase and HCV RNA values, suggesting
participation of virus-induced effector NK cells in
liver necroinflammation. Phenotypic changes in HCV
patients were associated with enhanced cytokine-induced
cytolytic activity and increased usage of natural cytotoxicity
and NKG2D receptor pathways, accompanied by
defective cytokine production, although to a lesser extent
than patients with chronic HBV infection. CONCLUSIONS:
These findings provide evidence for a functional
dichotomy in patients with chronic HBV and
HCV infections, featuring conserved or enhanced cytolytic
activity and dysfunctional cytokine production,
which may contribute to virus persistence.