title: The human fetal immune response to hepatitis C virus exposure in utero.
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 pro-inflammatory 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.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94143-1234, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Babik
authors.forename: Deborah
authors.initials: D
authors.lastname: Cohan
authors.forename: Alexander
authors.initials: A
authors.lastname: Monto
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Hartigan-O'Connor
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005315:Fetal Diseases / Q000276:immunology*; D053804:Granzymes / Q000097:blood; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000097:blood; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood; D007231:Infant, Newborn; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*
chemical_list: D016207:Cytokines; D018937:Hepatitis C Antibodies; D007075:Immunoglobulin M; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053804:Granzymes