Decreased frequency of HCV core-specific peripheral blood mononuclear cells with type 1 cytokine secretion in chronic hepatitis C.
OBJECTIVE
Since the outcome of hepatitis C infection appears to be correlated with the immune response to the HCV core protein, the aim of this study was to investigate the T cell response to hepatitis C virus core and core-derived antigens.


METHODS
As this response may be regulated importantly by differential secretion of cytokines, we determined the number of peripheral blood mononuclear cells (PBMC) that secreted IL-2, IL-4, IL-10, and IFN-gamma in response to a recombinant HCV core protein and a panel of 19 core-derived peptides, using the ELI-Spot-technique. Two groups of patients were studied: group A: 11 patients with previously self-limited HCV infection; group B: 12 patients with chronic hepatitis C.


RESULTS
In group B significantly less IFN-gamma spot forming cells (SFC) could be detected, both after stimulation with the core protein (0.083+/-0.083 SFC vs. 1.3+/-0.4 SFC/10(5) PBMC; p = 0.005 and with the core-derived peptides (1.3+/-0.5 vs. 4.4+/-1.1 SFC SFC/10(5) PBMC; p = 0.007). By analyzing the cytokine response to each single peptide, we found IFN-gamma responses to peptides aa 39-63 and aa 148-172 in group A but not in group B (p<0.03). In group B also, fewer IL-2 secreting cells were found after peptide stimulation (p = 0.04). Whereas subjects of group B showed IL-10-specific responses to HCV peptides more frequently than patients with self-limiting hepatitis C (p = 0.03), the number of IL-4-producing cells was not different between the two groups.


CONCLUSIONS
The data suggest that patients with persistent viremia and chronic liver disease (group B) have less PBMC showing type 1 cytokine (IL-2, IFN-gamma) responses to HCV core protein than patients with self-limited HCV infection (group A).
Lechmann
M
M
Department of Internal Medicine, University of Bonn, Germany.
Woitas
R P
RP
Langhans
B
B
Kaiser
R
R
Ihlenfeldt
H G
HG
Jung
G
G
Sauerbruch
T
T
Spengler
U
U
D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology*; D016174:Hepacivirus; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D018936:Hepatitis C Antigens; D011994:Recombinant Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus