Abstract
The proportions and activation status of T cells may influence responses to hepatitis C virus (HCV) and treatment outcome in patients receiving pegylated interferon (IFN)-alpha/ribavirin therapy. We confirmed that IFN-gamma enzyme-linked immunospot (ELISPOT) responses to HCV are poor in HCV patients and showed that responses to HCV and cytomegalovirus (CMV) antigens decrease during therapy. This was most apparent in patients with sustained virological response (SVR). Baseline frequencies of CD4+ effector memory (TEM) T cells were lower in SVR than non-SVR. Proportions of CD4+ and CD8+ TEM and terminally differentiated effector memory (TEMRA) T cells declined on therapy in SVR, as did proportions of Fas+ CD8+ TEMRA T cells. Baseline frequencies of programmed death (PD)-1-expressing CD4+ TEM and TEMRA T-cells were higher in SVR. Therapy increased percentages of PD-1+ CD4+ central memory (TCM) T cells and PD-1+ CD8+ TEM and TEMRA T cells in SVR. We conclude that successful therapy depletes circulating antigen-specific CD4+ T cell responses. This paralleled decreases in proportions of effector memory T cells and higher percentages of CD4+ TCM T cells expressing PD-1.
MeSH terms
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Adult
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Antigens, CD / analysis
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Antigens, Differentiation, T-Lymphocyte / analysis
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Antigens, Viral / immunology
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Antiviral Agents / administration & dosage
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Antiviral Agents / therapeutic use*
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Apoptosis Regulatory Proteins / analysis
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CD4-Positive T-Lymphocytes / chemistry
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / chemistry
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CD8-Positive T-Lymphocytes / immunology
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Cytomegalovirus / immunology
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Drug Therapy, Combination
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Female
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Hepacivirus / immunology*
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Hepatitis C Antigens / immunology*
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Hepatitis C, Chronic / blood
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Hepatitis C, Chronic / drug therapy
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Hepatitis C, Chronic / immunology*
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Humans
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Immunologic Memory*
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Interferon alpha-2
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Interferon-alpha / administration & dosage
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Interferon-alpha / therapeutic use*
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Interferon-gamma / metabolism
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Leukocytes / immunology*
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Lymphocyte Activation
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Lymphocyte Count
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Male
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Middle Aged
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Polyethylene Glycols / administration & dosage
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Polyethylene Glycols / therapeutic use*
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Programmed Cell Death 1 Receptor
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RNA, Viral / blood
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Recombinant Proteins
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Ribavirin / administration & dosage
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Ribavirin / therapeutic use*
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T-Lymphocyte Subsets / chemistry
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T-Lymphocyte Subsets / immunology*
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Young Adult
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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Antigens, Viral
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Antiviral Agents
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Apoptosis Regulatory Proteins
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Hepatitis C Antigens
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Interferon alpha-2
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Interferon-alpha
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PDCD1 protein, human
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Programmed Cell Death 1 Receptor
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RNA, Viral
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Recombinant Proteins
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Polyethylene Glycols
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Ribavirin
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Interferon-gamma
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peginterferon alfa-2a