Prenatal Sensitization in a Mouse Model

Several studies have suggested that the in utero environment plays an important role in the onset of sensitization to environmental allergens. This concept of in utero priming to favor the development of subsequent allergic diseases is supported by several observations. Already at birth cord blood mononuclear cells (CBMCs) proliferate in response to allergens such as Dermatophagoides pteronyssinus ( Der p ) or birch pollen (1–3). This allergen-specific immune response is mediated by fetal T cells, as opposed to maternally derived contaminants (4). Several factors remained crucial for the development of such a proliferative immune response. The mother must be exposed to the antigen beyond the first trimester of pregnancy (5, 6). The presence of allergen-specific IgE at birth also indicates the prenatal development of functional T–B cell interactions (7). This implies that the allergen responder phenotype may be determined by immune deviation involving allergendriven T cell selection. Such a notion is supported by finding that pregnancy is associated with a transient depression of maternal helper T cell type 1 (Th1)-mediated cell immunity, resulting in a Th2-like maternal profile at the maternal–fetal interface. Moreover, many studies have documented defective polyclonal interferon g (IFNg ) responses by CBMCs from neonates either at risk of atopy, or those who later develop disease (8–11). Our aim was to analyze the development of antigen-specific T and B cell responses in the preand postnatal immune system in a defined animal model of allergic sensitization. In this BALB/c mouse model, sensitization to ovalbumin (OVA) induces allergen-specific IgE/IgG 1 production associated with allergic response in the airway and increased airway hyperreactivity. This model was used to sensitize female BALB/c mice to OVA before their mating with nonsensitized BALB/c males. During pregnancy, mice were exposed to allergen aerosol every second day. Offspring T and B cell responses were analyzed at various time points after birth.