Hamzaoui Agnès, Ammar Jamel, Hamzaoui Kamel
Medicine Faculty, University of Tunis, Homeostasis and Cell Dysfunction (UR/99/08-40), Tunisia.
Multidiscip Respir Med. 2010 Feb 28;5(1):22-30. doi: 10.1186/2049-6958-5-1-22.
CD4+CD25+ regulatory T (Treg) cells play an essential role in maintaining immune homeostasis. In this study, we investigated whether the induced sputum (IS) pool and the function of CD4+CD25+ Treg cells are altered in asthma pediatric patients.
Treg activity was studied in the IS of 40 asthmatic children. CD3+ cells were analyzed for the expression of FoxP3 mRNA by real time reverse transcription-polymerase chain reaction (RT-PCR). IS cells from asthmatics and controls were stained for Treg markers and analyzed by flow cytometry. We also studied the ability of Treg cells to differentiate monocytes toward alternatively activated macrophages (AAM), and to suppress proinflammatory cytokines.
(i) Mild and moderate asthmatics had significantly decreased expression of FoxP3/β-actin mRNA and decreased proportions of CD4+CD25highFoxP3+ cells compared to healthy children; (ii) patients with moderate asthma had even lower proportions of FoxP3 expression compared to mild asthmatic patients; (iii) monocytes cultured with Treg cells displayed typical features of AAM, including up-regulated expression of CD206 (macrophage mannose receptor) and CD163 (hemoglobin scavenger receptor), and an increased production of chemokine ligand 18 (CCL18). In addition, Treg cells from asthmatics have a reduced capacity to suppress LPS-proinflammatory cytokine production from monocytes/macrophages (IL-1, IL-6 and TNF-α).
Asthma pediatric patients display a decreased bronchial Treg population. The impaired bronchial Treg activity is associated with disease severity.
CD4+CD25+调节性T（Treg）细胞在维持免疫稳态中起关键作用。在本研究中，我们调查了哮喘患儿诱导痰（IS）中CD4+CD25+ Treg细胞库及其功能是否发生改变。
对40例哮喘儿童的诱导痰中的Treg活性进行研究。通过实时逆转录-聚合酶链反应（RT-PCR）分析CD3+细胞中FoxP3 mRNA的表达。对哮喘患者和对照组的诱导痰细胞进行Treg标志物染色，并通过流式细胞术进行分析。我们还研究了Treg细胞将单核细胞分化为替代性活化巨噬细胞（AAM）以及抑制促炎细胞因子的能力。
（i）与健康儿童相比，轻度和中度哮喘患者FoxP3/β-肌动蛋白mRNA表达显著降低，CD4+CD25highFoxP3+细胞比例下降；（ii）与轻度哮喘患者相比，中度哮喘患者FoxP3表达比例更低；（iii）与Treg细胞共培养的单核细胞表现出AAM的典型特征，包括CD206（巨噬细胞甘露糖受体）和CD163（血红蛋白清除受体）表达上调，以及趋化因子配体18（CCL18）产生增加。此外，哮喘患者的Treg细胞抑制单核细胞/巨噬细胞LPS促炎细胞因子产生（IL-1、IL-6和TNF-α）的能力降低。
哮喘患儿支气管Treg细胞数量减少。支气管Treg活性受损与疾病严重程度相关。
