Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections.
OBJECTIVE
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-alpha and interferon-gamma 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.
Oliviero
Barbara
B
Research Laboratories, Fondazione I.R.C.C.S. Policlinico San Matteo and University of Pavia, Pavia, Italy.
Varchetta
Stefania
S
Paudice
Enrica
E
Michelone
Giuseppe
G
Zaramella
Marco
M
Mavilio
Domenico
D
De Filippi
Francesca
F
Bruno
Savino
S
Mondelli
Mario U
MU
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D019694:Hepatitis B, Chronic / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D037181:Lectins, C-Type; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D054341:Receptors, KIR3DL1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D037181:Lectins, C-Type; D052118:Lysosomal-Associated Membrane Protein 1; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054341:Receptors, KIR3DL1; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C515083:KIR3DL1 protein, human