Reduced naive CD4 T cell numbers and impaired induction of CD27 in response to T cell receptor stimulation reflect a state of immune activation in chronic hepatitis C virus infection

J Infect Dis. 2011 Mar 1;203(5):635-45. doi: 10.1093/infdis/jiq101. Epub 2011 Jan 10.

Abstract

Background: Chronic hepatitis C virus (HCV) infection is characterized by reduced numbers of functional HCV-specific T cells. In addition, chronically HCV-infected individuals have reduced response to vaccine. Alterations in naive CD4 T cell phenotype or function may contribute to these immune impairments.

Methods: Using flow cytometric analysis and enzyme-linked immunospot assay, we examined peripheral naive CD4 T cell phenotype and function in chronically HCV-infected patients and control subjects.

Results: We observed significantly lower absolute cell numbers of naive CD4 T cells in HCV-infected patients, localized to the CD127(+)CD25(low/-) and CD31(+) (RTE) subsets. Moreover, we found greater percentages of naive cells expressing CD25 and KI67 in HCV-infected patients, consistent with immune activation, further supported by higher plasma sCD27 levels. Functional analysis revealed an intact interferon-γ response to allogeneic B cell stimulus. However, after direct TCR stimulation, naive CD4 T cells from HCV-infected patients had altered up-regulation of KI67 and CD25 and less CD27 expression. The latter was associated with elevated baseline activation state. In addition, naive CD4 T cells from HCV-infected patients were more susceptible to cell death.

Conclusions: These numerical and functional defects may contribute to inadequate formation of virus and neoantigen-specific T cell responses during chronic HCV infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-gamma
  • Male
  • Middle Aged
  • Ohio
  • Receptors, Antigen, T-Cell / blood
  • Receptors, Antigen, T-Cell / immunology*
  • Risk Factors
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis*

Substances

  • Receptors, Antigen, T-Cell
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interferon-gamma