Epidemiology of Regulatory T Cells in Pregnancy and Childhood Atopic Diseases

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DESCRIPTION (provided by applicant): Childhood allergic diseases are a growing epidemic and are associated with considerable morbidity and mortality. Until now, most research has focused on postpartum exposures that may in part cause childhood allergic diseases. Unexplained findings related to birth order and recent findings on immunity in pregnancy have recently also pushed in utero programming (prenatal exposures) to the forefront in studies of causation. Thirty percent of cases of childhood allergic diseases have been attributed to a child's birth order. But, the underlying mechanism cannot be explained by the hygiene hypothesis, because there is little evidence of covariation of infection rates with birth order. Allergic status has been characterized by the T-helper1/T- helper2 ratio (Th1/Th2 ratio) skewed toward a Th2 cell-cytokine predominance, with the role of Th1 in the allergic response not yet defined. Pregnancy has also been assumed to be a Th2 dominant process. Thus pregnancy is likely a critical component in the causal web of childhood allergic diseases. Preliminary data indicate that T regulatory cells (Tregs), which suppress allogenic responses against the fetus in mice and humans, increase in successful pregnancy and decrease, but remain above prepregnancy levels, during the postpartum. Recent research has indicated that Tregs can control both Th1 and Th2 responses. Although a mode of tolerance transference from mother to fetus has not yet been identified, this could explain the effect of birth order on subsequent allergic risk that has been seen. Hence the question: what is the role of maternal Tregs during pregnancy in the risk of childhood allergic diseases? As part of an ongoing NIH- funded study, a cohort of pregnant women is being recruited for longitudinal study of their children at Henry Ford Health System to study the role of early life exposures in the development of childhood allergic disease (postnatal programming). Using a subset of 180 mother-child pairs from this ongoing cohort study, the following specific aims will be studied to detail the role of prenatal programming in childhood allergic disease: 1. Determine the relationships between maternal Tregs (CD4+CD25+CTLA4+ and CD4+CD25+FOXP3+ cells - counts and percentages) during pregnancy and: Tregs in their child's blood at delivery (cord), and 6 and 12 months; IgE in their child's blood at delivery (cord), and 6 and 12 months; and maternal IgE during pregnancy; 2. Quantify the within-woman change in Tregs from pregnancy (second trimester) throughout the postpartum period (1, 6 and 12 months postpartum); and 3. Determine the relationship between pregnancy history (prior pregnancy intervals and birth outcomes) and: maternal Tregs during pregnancy and 1, 6 and 12 months postpartum; and the child's Tregs at delivery (cord blood) and 6 and 12 months.