Dia-placental passage of nutritive and inhalative allergens

Research project P 14659 Dia-placental passage of nutritive and inhalative allergens Zsolt SZÉPFALUSI 09.10.2000 The prevalence of allergic diseases is currently rising at an unprecedented rate. Recently, concern has been raised as to a possible priming effect of prenatal exposure to environmental influences, i.e. through the placenta. Allergen-specific T cell proliferation in cord blood cells has been documented for many different nutritive and inhalative allergens. A line of evidence now supports the hypothesis that fetal T cells are exposed to maternally derived allergens during gestation. The immunological mechanisms involved in this process are not clear. A trans- amniotic transfer of maternal IgE antibodies and subsequent IgE-receptor mediated allergen-focusing has been postulated very recently Alternatively, a trans-placental allergen transfer may occur. In order to test this latter hypothesis, we designed a placenta perfusion model. The purpose of the herwith submitted study is on the one hand to investigate transfer and on the other hand transfer mechanisms of inhalative and nutritive allergens across the placenta with the help of a placenta model. In these experiments placentas (term and preterm) will be dually perfused after delivery at the maternal and fetal side. Soluble allergens are presented on the maternal side. The eluate on the fetal side will be collected and checked for the presence of the allergens. The following questions shall be addressed by our project: 1.) Do inhalative and nutritive allergens cross the placental barrier ? 2.) Are the kinetics of allergen transmission similar for nutritive and inhalative allergens ? 3.) Is allergen-transmission dose-dependent ? 4.) Is the diaplacental allergentransmission bound to or facilitated by the presence of immunoglobulin G ? 5.) Is a selective transport mechanism responsible for specific allergen-transfer? 6.) Is the diaplacental allergentransrmssion influenced by the time period (maturity) of pregnancy ? ,The answers deduced from these experiments shall help to understand, 1.) why T cell proliferation occurs in cord blood cells in response to common allergens, 2.) whether an allergic family history predisposes to facilitated dia- placental allergen transfer, 3.) what kind of immunologic mechanism is likely to explain the T cell priming effect in cord blood cells, a) anti-idiotypic antibodies triggering fetal/neonatal T and B cells or b) allergen/allergenic peptide presentation by antigen presenting cells (i.e. dendritic cells) in draining lymph nodes to circulating resting allergen-specific T cells. The final aim of all these experiments is to understand the mechanisms operative in prenatal allergen-specific T cell priming.