Ly Ngoc P, Ruiz-Perez Begona, McLoughlin Rachel M, Visness Cynthia M, Wallace Paul K, Cruikshank William W, Tzianabos Arthur O, O'Connor George T, Gold Diane R, Gern James E
Pediatric Pulmonary Medicine, University of California San Francisco Children's Hospital and UCSF Medical School, San Francisco, CA, USA.
Clin Mol Allergy. 2009 Jul 8;7:8. doi: 10.1186/1476-7961-7-8.
In the United States, asthma prevalence is particularly high among urban children. Although the underlying immune mechanism contributing to asthma has not been identified, having impaired T regulatory (Treg) cells at birth may be a determining factor in urban children. The objective of this study was to compare Treg phenotype and function in cord blood (CB) of newborns to those in peripheral blood (PB) of a subset of participating mothers.
Treg numbers, expression, and suppressive function were quantified in subjects recruited prenatally from neighborhoods where >/= 20% of families have incomes below the poverty line. Proportion of Treg cells and expression of naïve (CD45RA) or activated (CD45RO, CD69, and HLA-DR) markers in CD4+T cells was measured by flow cytometry. Treg suppressive capacity was determined by quantifying PHA-stimulated lymphocyte proliferation in mononuclear cell samples with and without CD25 depletion.
In an urban cohort of 119 newborns and 82 mothers, we found that newborns had similar number of cells expressing FOXP3 as compared to the mothers but had reduced numbers of CD4+CD25+bright cells that predominantly expressed the naïve (CD45RA) rather than the activated/memory (CD45RO) phenotype found in the mothers. Additionally, the newborns had reduced mononuclear cell TGF-beta production, and reduced Treg suppression of PHA-stimulated lymphocyte proliferation compared to the mothers.
U.S. urban newborns have Treg cells that express FOXP3, albeit with an immature phenotype and function as compared to the mothers. Longitudinal follow-up is needed to delineate Treg cell maturation and subsequent risk for atopic diseases in this urban birth cohort.
在美国，城市儿童哮喘患病率特别高。尽管导致哮喘的潜在免疫机制尚未明确，但出生时调节性T（Treg）细胞功能受损可能是城市儿童患哮喘的一个决定性因素。本研究的目的是比较新生儿脐带血（CB）与部分参与研究母亲外周血（PB）中Treg细胞的表型和功能。
对产前从家庭收入≥20%低于贫困线的社区招募的受试者的Treg细胞数量、表达和抑制功能进行定量分析。通过流式细胞术检测CD4+T细胞中Treg细胞的比例以及幼稚（CD45RA）或活化（CD45RO、CD69和HLA-DR）标志物的表达。通过定量有无CD25去除的单核细胞样本中PHA刺激的淋巴细胞增殖来确定Treg细胞的抑制能力。
在一个由119名新生儿和82名母亲组成的城市队列中，我们发现新生儿表达FOXP3的细胞数量与母亲相似，但CD4+CD25+高表达细胞数量减少，这些细胞主要表达幼稚（CD45RA）而非母亲中发现的活化/记忆（CD45RO）表型。此外，与母亲相比，新生儿的单核细胞TGF-β产生减少，Treg细胞对PHA刺激的淋巴细胞增殖的抑制作用降低。
美国城市新生儿有表达FOXP3的Treg细胞，尽管其表型和功能与母亲相比不成熟。需要进行纵向随访以描述该城市出生队列中Treg细胞的成熟情况以及随后患特应性疾病的风险。
