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.
AMC Liver Center, Department of Gastroenterology and Hepatology, University of Amsterdam, Amsterdam, The Netherlands. ellie.barnes@ndm.ox.ac.uk
Eleanor
E
Barnes
Huub C
HC
Gelderblom
Isla
I
Humphreys
Nasser
N
Semmo
Henk W
HW
Reesink
Marcel G H M
MG
Beld
René A W
RA
van Lier
Paul
P
Klenerman
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