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. 2010 Nov;7(6):454-8.
doi: 10.1038/cmi.2010.34. Epub 2010 Jul 26.

Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg+/HBeAg- mothers

Lemonica Koumbi  1 , Antonio Bertoletti, Vassiliki Anastasiadou, Maria Machaira, Winnie Goh, Nikolaos G Papadopoulos, Dimitris A Kafetzis, Vassiliki Papaevangelou
Affiliations

Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg+/HBeAg- mothers

Lemonica Koumbi et al. Cell Mol Immunol. 2010 Nov.

Abstract

Vertically transmitted hepatitis B virus (HBV) usually causes chronic infection. While combined active-passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive (HBsAg(+)) mothers at birth prevents vertical transmission, it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen (HBeAg). This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg(+)/HBeAg(-) mothers. Blood was collected from 46 HBsAg(+) mothers and their neonates (subjects) as well as 24 age-matched controls. All neonates of HBsAg(+) mothers received appropriate immunoprophylaxis, and HBsAg and hepatitis B surface antibody (anti-HBs) antibody titers were determined after completion of the vaccination course. Peripheral blood mononuclear cells (PBMCs) from infants at birth, 1 and 6 months of age were stimulated with recombinant HBsAg, hepatitis B core antigen (HBcAg) and mitogen, and interferon (IFN)-γ concentrations were determined by ELISA. HBsAg-induced production of IL-2, IL-5, IL-6 and IL-10 was assessed using a cytometric bead array kit on cells from 6-month-old neonates post-vaccination. All neonates were HBsAg(-) and responded to vaccination. Increased IFN-γ production following HBcAg stimulation was seen in 30.4% of neonates born to HBsAg(+)/HBeAg(-) mothers. Subjects demonstrated significantly higher IL-2 production post-HBsAg stimulation, whereas IL-5, IL-6 and IL-10 cytokine responses were not significantly different. Almost one-third of uninfected neonates developed viral antigen-induced IFN-γ production, suggesting that they had been exposed to virions or viral derivatives. This encounter, however, did not impair their T-cell responses to vaccination.

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Figures

Figure 1
Figure 1
In vitro IFN-γ production from PBMCs in subjects and controls. PBMC secretion of IFN-γ after a 72-h incubation with PHA (a), HBcAg (b) and HBsAg (c) from 23 neonatal subjects born to HBsAg+ mothers (•) and 24 neonatal controls (○) at birth, 1 and 6 months of age. The data were compared by Mann–Whitney test: no significant differences were found between the two groups (P>0. 005). Each dot represents a single donor and horizontal bars represent the mean values. HBcAg, hepatitis B core antigen; HBsAg, hepatitis B surface antigen; IFN, interferon; PBMC, peripheral blood mononuclear cell; PHA, phytohemagglutinin.
Figure 2
Figure 2
IFN-γ secretion by PBMCs of subjects that responded to HBcAg stimulation. The percentages of responders as well as the secreted IFN-γ levels from PBMCs after a 72-h incubation with HBcAg at birth, 1 and 6 months of age are shown. HBcAg, hepatitis B core antigen; IFN, interferon; PBMC, peripheral blood mononuclear cell.
Figure 3
Figure 3
In vitro cytokine production from PBMCs after HBsAg stimulation in 6-month-old subjects and controls. PBMC secretion of IL-2, IL-5, IL-6 and IL-10 after a 72-h incubation with HBsAg from eight neonatal subjects born to HBsAg+ mothers (•) and five neonatal controls (○) at 6 months of age. The data were compared by Mann–Whitney test: IL-2 expression was significantly higher in the subject group compared to the control group (P<0.005). Each dot represents a single donor and horizontal bars represent the mean values. HBsAg, hepatitis B surface antigen; PBMC, peripheral blood mononuclear cell.
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