Cellular immune responses during high-dose interferon-alpha induction therapy for hepatitis C virus infection.
BACKGROUND
The effect that high-dose interferon (IFN)-alpha induction therapy for hepatitis C virus (HCV) infection has on cellular immune responses is currently unknown.


METHODS
Thirty-one treatment-naive patients with chronic HCV infection received amantadine and ribavirin, combined with 6 weeks of high-dose IFN-alpha-2b induction therapy followed by weekly pegylated IFN-alpha-2b, for 24 or 48 weeks. Using IFN-gamma and interleukin (IL)-2 enzyme-linked immunospot (ELISpot) assays, we analyzed the pattern of cytokine secretion by structural and nonstructural HCV- and cytomegalovirus (CMV)-specific T cells before, during, and after therapy.


RESULTS
HCV-specific T cell responses, which were predominantly IFN-gamma secreting and which correlated with alanine transaminase levels (r2 = 0.45; P = .001), were found before treatment in 10 of 15 patients with a sustained virological response (SVR) and in 11 of 16 in the non-SVR group. There was a striking loss of IFN-gamma and IL-2 HCV-specific T cells during therapy, predominantly in the SVR group. This response recovered after cessation of therapy, regardless of outcome. Suppression of CMV-specific T cell responses, in addition to total lymphocyte counts, was also observed.


CONCLUSIONS
High-dose IFN-alpha induction therapy leads to a profound decline in IL-2- and IFN-gamma-secreting HCV- and CMV-specific T cells. These data indicate that restoration of T cell responses is unlikely to be causally linked to an early response or SVR to therapy.
Barnes
Eleanor
E
AMC Liver Center, Department of Gastroenterology and Hepatology, University of Amsterdam, Amsterdam, The Netherlands. ellie.barnes@ndm.ox.ac.uk
Gelderblom
Huub C
HC
Humphreys
Isla
I
Semmo
Nasser
N
Reesink
Henk W
HW
Beld
Marcel G H M
MG
van Lier
René A W
RA
Klenerman
Paul
P
D000328:Adult; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
D000998:Antiviral Agents; D016898:Interferon-alpha