The Human Fetal Immune Response to Hepatitis C Virus Exposure in Utero

Journal of Infectious Diseases 
Volume203, Issue2
Pp. 196-206.

Jennifer M. Babik 1,2, Deborah Cohan 3, Alexander Monto 4, Dennis J. Hartigan-O'Connor 1 and Joseph M. McCune 1

+ Author Affiliations

1 Division of Experimental Medicine
2 Division of Infectious Diseases, Department of Medicine, University of California, San Francisco
3 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco and San Francisco General Hospital
4 Division of Gastroenterology, Department of Medicine, University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, San Francisco, California

Reprints or correspondence: Dr Joseph M. McCune, Division of Experimental Medicine, Department of Medicine, Box 1234, University of California, San Francisco, San Francisco, CA 94143-1234 (mike.mccune@ucsf.edu).

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.

Footnotes

Potential conflicts of interest: none reported.

Financial support: This work was supported in part by a Ruth L. Kirschstein National Research Service Award (T32 AI007641-06A2 to J.M.B), a Pilot/Feasibility grant from the UCSF Liver Center (P30 DK026743 to J.M.M.), NIH/NCRR UCSF - CTSI Grant Number UL1 RR024131, a grant to the UCSF - GIVI Center for AIDS Research (P30 AI027763), and the Harvey V. Berneking Living Trust. J.M.M. is a recipient of the NIH Director's Pioneer Award Program, part of the NIH Roadmap for Medical Research, through grant DPI OD00329.

The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

The information in this manuscript has not been presented previously at any meeting.

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