Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C.
OBJECTIVE
Acute hepatitis C virus (HCV) infection becomes chronic in the majority of patients. Although HCV-specific CD4 T-cell response is associated with HCV clearance, less is known about virus-specific CD8 T-cell or neutralizing antibody (nAb) responses and the role of CD4 help in their induction during acute infection.


METHODS
HCV-specific CD4, CD8, and HCV pseudoparticle (HCVpp) nAb responses were monitored in acutely HCV-infected patients to define their relative contributions to viral clearance.


RESULTS
Our results show that the outcome of acute hepatitis C is associated with a functional hierarchy in HCV-specific CD4 T-cell response and the scope of virus-specific, total T-cell interferon-gamma response. HCV-specific CD8 T-cell response was readily detectable in acutely HCV-infected patients regardless of virologic outcome or virus-specific CD4 T-cell response. In contrast, HCVpp-specific nAbs were readily detected in patients with chronic evolution and impaired virus-specific CD4 T-cell response but not in patients who cleared infection with robust virus-specific CD4 T-cell response.


CONCLUSIONS
The outcome of acute hepatitis C is associated with efficient virus-specific CD4 T-cell response(s) without which HCV-specific CD8 T-cell and heterologous nAb responses may develop but fail to clear viremia. Furthermore, HCV-specific nAb responses may not be induced despite robust virus-specific CD4 T-cell response.
Kaplan
David E
DE
Gastroenterology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Sugimoto
Kazushi
K
Newton
Kimberly
K
Valiga
Mary E
ME
Ikeda
Fusao
F
Aytaman
Ayse
A
Nunes
Frederick A
FA
Lucey
Michael R
MR
Vance
Barbara A
BA
Vonderheide
Robert H
RH
Reddy
K Rajender
KR
McKeating
Jane A
JA
Chang
Kyong-Mi
KM
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D014481:United States; D014771:Virion / Q000276:immunology
D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D007371:Interferon-gamma