Interferon-α-induced CD100 on naïve CD8 + T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction

J Int Med Res. 2017 Feb;45(1):89-100. doi: 10.1177/0300060516676136. Epub 2017 Jan 12.

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

  • Adult
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Antigens, Differentiation, B-Lymphocyte / genetics*
  • Antigens, Differentiation, B-Lymphocyte / immunology
  • Antiviral Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Case-Control Studies
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • Female
  • Gene Expression Regulation
  • Hepacivirus / drug effects
  • Hepacivirus / growth & development
  • Hepacivirus / immunology
  • Hepatitis C / drug therapy*
  • Hepatitis C / immunology
  • Hepatitis C / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Primary Cell Culture
  • RNA, Viral / drug effects
  • Recombinant Proteins / therapeutic use
  • Semaphorins / genetics*
  • Semaphorins / immunology
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • Antiviral Agents
  • CD100 antigen
  • CD72 protein, human
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Semaphorins
  • Tumor Necrosis Factor-alpha
  • Polyethylene Glycols
  • Interferon-gamma
  • peginterferon alfa-2a