The human fetal immune response to hepatitis C virus exposure in utero

Jennifer M. Babik, Deborah Cohan, Alexander Monto, Dennis J. Hartigan-O'Connor, Joseph M. McCune

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background. Although the rate of mother-to-child transmission of hepatitis C virus (HCV) is low, the effect of HCV exposure in utero on the fetal immune system is unknown. Methods. Umbilical cord blood was obtained from 7 neonates born to HCV-seropositive, HCV RNA-positive women and 8 neonates born to HCV-seronegative women. Cord blood mononuclear cells were analyzed by immunophenotyping and by intracellular cytokine staining after HCV-specific and polyclonal stimulation. Plasma was analyzed for anti-HCV immunoglobulin M (IgM), cytokine/granzyme concentrations, and indoleamine 2,3-dioxygenase (IDO) activity. Results. HCV-exposed neonates had significantly lower levels of regulatory T cells expressing HLA-DR, lower CD4+ and CD8+ T cell activation, and lower plasma levels of pro-inflammatory markers than did controls. However, CD4+ and CD8+ T cells from HCV-exposed neonates had higher IFN-γ production in response to polyclonal stimulation than did T cells from controls. IDO activity was similar between groups. No HCV-specific T cell responses or anti-HCV IgM were detected in any neonates. Conclusions. HCV-exposed neonates showed a relative suppression of immune activation and proinflammatory markers, which was counterbalanced by an increased production capacity for IFN-γ. These results suggest that HCV encounters the fetal immune system in utero, and alters the balance between suppressive and pro-inflammatory responses.

Original languageEnglish (US)
Pages (from-to)196-206
Number of pages11
JournalJournal of Infectious Diseases
Volume203
Issue number2
DOIs
StatePublished - Jan 15 2011

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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