Abstract

BackgroundAllergy has been an increasing problem in several parts of the world. Prenatal exposure to allergen and microbial components may affect the development of allergies in childhood, as indicated by epidemiological and experimental studies. We investigated the capacity for allergic sensitisation in offspring after induction of a Th1- or a Th2-polarised immune response to the same allergen in mothers during pregnancy.ResultsDuring pregnancy, mice were immunised with ovalbumin (OVA) given with either one of the Th2-adjuvants pertussis toxin (PT) or Al(OH)3 (aluminium hydroxide), or with the Th1 adjuvant CpG. Offspring were immunised with OVA in Al(OH)3 as young adults. Serum and supernatants from ex vivo stimulated or non-stimulated spleen cells from mothers and offspring were analysed for OVA-specific antibodies and cytokines, respectively. Mothers immunised with OVA together with either Al(OH)3 or PT had increased levels of OVA-specific IgE and IgG1 compared to naive mothers, whereas mothers immunised with OVA together with CpG had increased levels of OVA-specific IgG2a compared to naive mothers. In general the highest levels of IL-5, IL-10, and IFNγ were observed in spleen cells from mothers immunised with PT and OVA. Upon immunisation, offspring from mothers immunised with OVA and either PT or Al(OH)3 showed reduced levels of OVA-specific IgE and IgG1 and increased levels of OVA-specific IgG2a antibodies compared to offspring from naive mothers. Maternal immunisation with CpG and OVA did not affect antibody responses in offspring.ConclusionAllergic sensitisation in the offspring was affected by the type of adjuvant used for immunisation of the mothers with the same allergen. Th2 polarisation of the immune response in the mothers was found to give reduced IgE levels upon sensitisation of the offspring, whereas no reduction was achieved with Th1 polarisation in the mothers.

Highlights

  • Allergy has been an increasing problem in several parts of the world

  • Antibody and cytokine responses in mothers immunized with OVA and pertussis toxin (PT), cytosine-guanine dinucleotides (CpG), or Al(OH)3 First, we examined whether the adjuvants used had induced a Th1- or Th2-dominant immune response in the mothers as intended

  • Blood samples were taken from the mothers on day 3 of pregnancy (T0) to determine antibody levels before immunisation, at 10 days after delivery (T10), and at the end of the lactation period (TT) (Table 1)

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Summary

Introduction

Allergy has been an increasing problem in several parts of the world. Prenatal exposure to allergen and microbial components may affect the development of allergies in childhood, as indicated by epidemiological and experimental studies. Allergen-specific immune responses in cord blood mononuclear cells (CBMCs) have been detected already at 22 weeks of gestation [1]. Reduced mitogen- and allergen-induced IFNg secretion in CBMCs has been reported in children who subsequently developed allergy [3,4]. Increased total cord blood IgE levels has been reported in children who develop allergy later in life [6,7]. If the immune system can be primed in utero for development of allergy, prevention of allergic disease should start before birth

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