Abstract
Objectives We investigated the effects of CD100 on naïve CD8+ T cells during hepatitis C virus (HCV) infection after interferon-α (IFN-α) therapy to clarify the mechanism underlying the effect of IFN-α in enhancing the antiviral response. Methods The CD100 molecules on subsets of CD8+ T cells were analysed with flow cytometry. The effects of CD100-overexpressing naïve CD8+ T cells were determined with ELISAs and an MTT cytotoxicity assay. The role of CD100-CD72 signal transduction was analysed with a neutralization and transwell assays. Results HCV infection reduced CD100 expression on CD8+ T cells, whereas IFN-α treatment significantly increased CD100 expression on naïve CD8+ T cells. The increased CD100 interacted with the CD72 receptor and enhanced PBMC cytokine secretion (IFN-γ and tumour necrosis factor-α) and cytotoxicity. Conclusions IFN-α-induced CD100 on naïve CD8+ T cells promotes PBMC cytokine secretion and cytotoxicity through CD100-CD72 signalling during HCV infection.
Keywords:
CD100; IFN-α therapy; hepatitis C; naïve CD8+ T cell.
MeSH terms
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Adult
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Antigens, CD / genetics*
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Antigens, CD / immunology
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Antigens, Differentiation, B-Lymphocyte / genetics*
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Antigens, Differentiation, B-Lymphocyte / immunology
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Antiviral Agents / therapeutic use*
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CD8-Positive T-Lymphocytes / drug effects*
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / virology
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Case-Control Studies
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Coculture Techniques
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Cytotoxicity, Immunologic
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Female
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Gene Expression Regulation
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Hepacivirus / drug effects
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Hepacivirus / growth & development
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Hepacivirus / immunology
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Hepatitis C / drug therapy*
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Hepatitis C / immunology
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Hepatitis C / virology
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Humans
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Interferon-alpha / therapeutic use*
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Interferon-gamma / genetics
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Interferon-gamma / immunology
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / virology
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Male
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Middle Aged
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Polyethylene Glycols / therapeutic use*
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Primary Cell Culture
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RNA, Viral / drug effects
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Recombinant Proteins / therapeutic use
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Semaphorins / genetics*
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Semaphorins / immunology
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Signal Transduction
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
Substances
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Antigens, CD
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Antigens, Differentiation, B-Lymphocyte
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Antiviral Agents
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CD100 antigen
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CD72 protein, human
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Interferon-alpha
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RNA, Viral
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Recombinant Proteins
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Semaphorins
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Tumor Necrosis Factor-alpha
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Polyethylene Glycols
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Interferon-gamma
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peginterferon alfa-2a