Host immune responses in hepatitis C virus clearance.
OBJECTIVE
The factors that determine the outcome of hepatitis C virus (HCV) infection are not fully understood. An increased and broadly targeted/multispecific T-cell response is thought to be paramount to a favourable outcome. Human leucocyte antigen (HLA) genes, in particular DRB1 and DQB1, are also reported to influence outcome of infection. We have previously demonstrated strong associations between DRB10101 and spontaneous viral clearance. The aim of the current study was to investigate HCV-specific T-cell response and the influence of DRB10101 in patients with long-term history of HCV clearance as compared to patients that developed persistent HCV infection.


METHODS
The proliferation of peripheral blood mononuclear cells stimulated with five non-structural and core HCV antigens and 20 synthesized HCV peptides, designed using T-cell epitope-predictive software, was determined by the incorporation of H-thymidine.


RESULTS
Although HCV-specific T-cell responses were more frequently detected and a broader range of peptides were targeted in the viral clearance group, the magnitude and breadth of the responses were not significantly different to that in the viral persistence group. The magnitude and breadth of the T-cell response was significantly associated, however, with possession of DRB10101. Furthermore DRB10101 positive individuals with viral clearance had broader HCV-specific T-cell responses.


CONCLUSIONS
These findings lend further credence to the importance of the host immune system to the outcome of HCV infection and provide a rationale for the role of DRB10101 in the resolution of HCV infection.
Barrett
Sharon
S
Centre for Liver Disease, Mater Misericordiae University Hospital, Dublin 7, Ireland.
Sweeney
Michael
M
Crowe
John
J
D002478:Cells, Cultured; D015234:HLA-A Antigens / Q000032:analysis / Q000235:genetics; D059811:HLA-DRB1 Chains; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000821:virology; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology / Q000821:virology; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012075:Remission, Spontaneous; D013601:T-Lymphocytes / Q000276:immunology
D015234:HLA-A Antigens; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen; D018936:Hepatitis C Antigens; D010446:Peptide Fragments; D011994:Recombinant Proteins