Epidemiology of Regulatory T Cells in Pregnancy and Childhood Atopic Diseases

描述（由申请人提供）：儿童过敏性疾病是一种日益增长的流行病，并与相当大的发病率和死亡率相关。到目前为止，大多数研究都集中在产后暴露，可能部分导致儿童过敏性疾病。与出生顺序有关的无法解释的发现和最近关于怀孕免疫的发现最近也将子宫内编程（产前暴露）推到了因果关系研究的最前沿。30%的儿童过敏性疾病病例归因于孩子的出生顺序。但是，基本的机制不能用卫生假说来解释，因为几乎没有证据表明感染率与出生顺序存在协变。过敏状态的特征在于T辅助细胞1/T辅助细胞2比率（Th 1/Th 2比率）偏向于Th 2细胞-细胞因子优势，而Th 1在过敏反应中的作用尚未确定。妊娠也被认为是Th 2占主导地位的过程。因此，怀孕可能是儿童过敏性疾病因果网络的关键组成部分。初步数据表明，调节性T细胞（T细胞），抑制同种异体反应对胎儿在小鼠和人类，增加成功怀孕和减少，但保持高于孕前水平，在产后。最近的研究表明，Tactobacillus可以控制Th 1和Th 2反应。虽然尚未确定从母亲到胎儿的耐受性转移模式，但这可以解释出生顺序对随后的过敏风险的影响。因此，问题是：在儿童过敏性疾病的风险中，母亲在怀孕期间的甲状腺激素的作用是什么？作为NIH资助的一项正在进行的研究的一部分，一组孕妇正在被招募，在亨利福特卫生系统对她们的孩子进行纵向研究，以研究早期生活暴露在儿童过敏性疾病发展中的作用（出生后编程）。使用来自这项正在进行的队列研究的180对母子对的子集，将研究以下具体目标以详细说明产前规划在儿童过敏性疾病中的作用：1.确定妊娠期间母体T淋巴细胞（CD 4 + CD 25 + CTLA 4+和CD 4 + CD 25 + FOXP 3+细胞-计数和百分比）与以下各项之间的关系：分娩时（脐带）以及6个月和12个月时其子女血液中的T淋巴细胞;分娩时（脐带）以及6个月和12个月时其子女血液中的IgE;以及妊娠期间母体IgE; 2.量化从怀孕（第二孕期）到整个产后期（产后1、6和12个月）的TdR的妇女内变化;以及3.确定怀孕史（以前的怀孕间隔和出生结果）之间的关系：母亲在怀孕期间和产后1个月，6个月和12个月的甲状腺激素;和孩子的甲状腺激素在分娩（脐带血）和6个月和12个月。

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.