TY - JOUR
T1 - The dynamics of T-lymphocyte responses during combination therapy for chronic hepatitis C virus infection
AU - Barnes, Eleanor
AU - Harcourt, Gillian
AU - Brown, Dave
AU - Lucas, Michaela
AU - Phillips, Rodney
AU - Dusheiko, Geoffrey
AU - Klenerman, Paul
PY - 2002/1/1
Y1 - 2002/1/1
N2 - Hepatitis C virus (HCV) readily sets up a persistent infection and is a major cause of liver disease worldwide. Interferon alfa and ribavirin therapy lead to sustained clearance of virus in 31% to 64% of patients with type 1 and non-type 1 genotypes, respectively. It is not clear to what extent these drugs act directly to reduce HCV replication, or indirectly via host immune responses, and what evoked immune responses are associated with clinical outcome. We have examined prospectively 15 patients with chronic HCV infection before, during, and after combination therapy. Quantitative assays for HCV antigen-specific CD4+ and CD8+ T-cell responses, and flow cytometric assays for analysis of the phenotype of T cells, in addition to viral sequencing of core protein, were performed throughout the treatment and follow-up period over 18 months. We found enhancement of proliferative T-cell responses during therapy. Proliferative responses are strikingly heterogeneous in terms of specificity, kinetics, and magnitude. Proliferative responses are often not associated with interferon-γ release. T-cell responses are rarely sustained irrespective of treatment outcome and this is not due to the evolution of new immune escape variants. T-cell responses tend to peak late in the course of treatment. In conclusion, combination therapy for HCV has a transient effect on host virus-specific T cells in the blood. Induction of sustained T-cell responses may require additional immune modulation later in therapy.
AB - Hepatitis C virus (HCV) readily sets up a persistent infection and is a major cause of liver disease worldwide. Interferon alfa and ribavirin therapy lead to sustained clearance of virus in 31% to 64% of patients with type 1 and non-type 1 genotypes, respectively. It is not clear to what extent these drugs act directly to reduce HCV replication, or indirectly via host immune responses, and what evoked immune responses are associated with clinical outcome. We have examined prospectively 15 patients with chronic HCV infection before, during, and after combination therapy. Quantitative assays for HCV antigen-specific CD4+ and CD8+ T-cell responses, and flow cytometric assays for analysis of the phenotype of T cells, in addition to viral sequencing of core protein, were performed throughout the treatment and follow-up period over 18 months. We found enhancement of proliferative T-cell responses during therapy. Proliferative responses are strikingly heterogeneous in terms of specificity, kinetics, and magnitude. Proliferative responses are often not associated with interferon-γ release. T-cell responses are rarely sustained irrespective of treatment outcome and this is not due to the evolution of new immune escape variants. T-cell responses tend to peak late in the course of treatment. In conclusion, combination therapy for HCV has a transient effect on host virus-specific T cells in the blood. Induction of sustained T-cell responses may require additional immune modulation later in therapy.
UR - http://www.scopus.com/inward/record.url?scp=0036727325&partnerID=8YFLogxK
U2 - 10.1053/jhep.2002.35344
DO - 10.1053/jhep.2002.35344
M3 - Article
C2 - 12198669
AN - SCOPUS:0036727325
SN - 0270-9139
VL - 36
SP - 743
EP - 754
JO - Hepatology
JF - Hepatology
IS - 3
ER -