Immunobiology 219 (2014) 377–384 Contents lists available at ScienceDirect Immunobiology jo ur nal ho me page: www.elsevier.com/locate/imbio Tolerogenic microenvironment in neonatal period induced by maternal immunization with ovalbumin Bruno Pacola Muniz a , Jefferson Russo Victor a , Luana de Mendonc ¸ a Oliveira a , Aline Aparecida de Lima Lira a , Adenir Perini b , Clarice Rosa Olivo b , Fernanda Magalhães Arantes-Costa b , Milton Arruda Martins b , Alberto José da Silva Duarte a , Maria Notomi Sato a,∗ a Laboratory of Medical Investigation, LIM 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil b Department of Medicine, LIM 20, Medical School, University of São Paulo, São Paulo, Brazil a r t i c l e i n f o Article history: Received 22 October 2013 Received in revised form 5 December 2013 Accepted 3 January 2014 Available online 10 January 2014 Keywords: Allergy Maternal antibodies Neonatal Dendritic cells Regulatory T cells a b s t r a c t Maternal immunization with allergens, such as ovalbumin (OVA), can inhibit the development of an allergic response in offspring. The regulatory mechanisms seem to be mediated by maternal antibod- ies (MatAbs) and factors generated by the maternal–fetal interface. The aim of this study was to verify the pathways of inhibitory Ab transference after maternal immunization with OVA and the effect of the offspring’s dendritic cells (DCs) on the generation of regulatory T (Treg) cells. We verified that precon- ceptional OVA immunization induces high levels of proinflammatory and regulatory cytokines in the amniotic fluid, allowing the transference of high levels of anti-OVA IgG1 Abs to the offspring. Using an adoptive nursing protocol, we verified that maternal immunization leads to MatAb transference by the placental route and by breastfeeding contribute to the inhibition of anaphylactic IgE and IgG1 Ab responses in immunized offspring. We observed that maternal immunization decreased eosinophil num- bers in recovered bronchoalveolar lavage fluid and in the lung tissue, whereas with a lack of control of airway responsiveness to methacholine. Maternal immunization induced in young offspring a decreased percentage of CD11c+ DCs expressing MHC class II and CD40 molecules. Moreover, DCs from both groups of offspring when pulsed with OVA, were able to induce Treg cells in vitro. Similarly, OVA immunization at the neonatal stage increased the frequency of Treg cells, regardless of the mother’s immunization sta- tus. These findings emphasize that maternal immunization leads to a complex interaction of regulatory factors, with MatAbs, DCs and Treg cells affecting the tolerance of offspring during an allergic response. © 2014 Elsevier GmbH. All rights reserved. Introduction Early postnatal exposure to an allergen has been shown to enhance the risk of subsequent allergic reactivity to the same aller- gen in adult life (Warner, 2004). The hypothesis that early events occurring during fetal development and/or in childhood could determine allergic disease in adulthood is supported by clinical and epidemiological observations (Prescott et al., 2006). For these reason is relevant to investigate maternal vaccination strategies Abbreviations: MatAb, maternal antibodies; d-o, day old; OVA, ovalbumin; Treg, regulatory T cells; PCA, passive cutaneous anaphylaxis. ∗ Corresponding author at: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Medical School of the University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 500, 3rd Floor, 05403-000 São Paulo, Brazil. Tel.: +55 11 30617499; fax: +55 11 30817190. E-mail address: marisato@usp.br (M.N. Sato). to prevent early allergic responses due to post-natal allergen exposure. Neonatal defense against bacterial, viral, protozoan and fun- gal infections in utero or after delivery is dependent on maternal immunity because neonates lack immunological memory and often have a slower capacity to develop immune responses (Adkins et al., 2004; Marodi, 2006; Levy, 2007; Futata et al., 2012). The neonatal dendritic cell (DC) system is often immature and exhibits decreased production of Th1-polarizing cytokines and is thus biased toward Th2-type responses (Adkins et al., 2004; Levy, 2007). While the neonatal immune system is immature, the system is highly plastic, and mature immune function can be achieved in certain specialized circumstances, e.g. BCG vaccination (Adkins et al., 2004). Moreover, maternal antibodies (MatAbs) can shape the B cell repertoire of the offspring long after the MatAbs themselves become undetectable (Fink et al., 2008). Preconceptional immunization with allergens has shown an interesting ability to efficiently inhibit IgE development in offspring (Fusaro et al., 2002; Victor et al., 2003). A schedule of maternal 0171-2985/$ – see front matter © 2014 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.imbio.2014.01.002