Full-breadth analysis of CD8+ T-cell responses in acute hepatitis C virus infection and early therapy
Standard
Full-breadth analysis of CD8+ T-cell responses in acute hepatitis C virus infection and early therapy. / Lauer, Georg M; Lucas, Michaela; Timm, Joerg; Ouchi, Kei; Kim, Arthur Y; Day, Cheryl L; Schulze Zur Wiesch, Julian; Paranhos-Baccala, Glaucia; Sheridan, Isabelle; Casson, Deborah R; Reiser, Markus; Gandhi, Rajesh T; Li, Bin; Allen, Todd M; Chung, Raymond T; Klenerman, Paul; Walker, Bruce D.
In: J VIROL, Vol. 79, No. 20, 10.2005, p. 12979-12988.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Full-breadth analysis of CD8+ T-cell responses in acute hepatitis C virus infection and early therapy
AU - Lauer, Georg M
AU - Lucas, Michaela
AU - Timm, Joerg
AU - Ouchi, Kei
AU - Kim, Arthur Y
AU - Day, Cheryl L
AU - Schulze Zur Wiesch, Julian
AU - Paranhos-Baccala, Glaucia
AU - Sheridan, Isabelle
AU - Casson, Deborah R
AU - Reiser, Markus
AU - Gandhi, Rajesh T
AU - Li, Bin
AU - Allen, Todd M
AU - Chung, Raymond T
AU - Klenerman, Paul
AU - Walker, Bruce D
PY - 2005/10
Y1 - 2005/10
N2 - Multispecific CD8(+) T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8(+) T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8(+) T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8(+) T-cell responses, as well as CD4(+) T-cell responses. Rapid recrudescence also occurred despite broad CD8(+) T-cell responses. Importantly, in vivo suppression of CD3(+) T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8(+) T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses.
AB - Multispecific CD8(+) T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8(+) T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8(+) T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8(+) T-cell responses, as well as CD4(+) T-cell responses. Rapid recrudescence also occurred despite broad CD8(+) T-cell responses. Importantly, in vivo suppression of CD3(+) T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8(+) T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses.
KW - Acute Disease
KW - Antiviral Agents/therapeutic use
KW - CD4-Positive T-Lymphocytes/immunology
KW - CD8-Positive T-Lymphocytes/immunology
KW - Drug Therapy, Combination
KW - Epitopes, T-Lymphocyte/immunology
KW - Hepacivirus/chemistry
KW - Hepatitis C/drug therapy
KW - Humans
KW - Interferon alpha-2
KW - Interferon-alpha/therapeutic use
KW - Lymphocyte Activation
KW - Polyethylene Glycols/therapeutic use
KW - Recombinant Proteins
KW - Ribavirin/therapeutic use
KW - Up-Regulation
KW - Viral Proteins/immunology
U2 - 10.1128/JVI.79.20.12979-12988.2005
DO - 10.1128/JVI.79.20.12979-12988.2005
M3 - SCORING: Journal article
C2 - 16189000
VL - 79
SP - 12979
EP - 12988
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 20
ER -