Department of Paediatrics, Tokyo Metropolitan Ebara Hospital, Tokyo, Japan.
Int Arch Allergy Immunol. 2011;156(2):148-58. doi: 10.1159/000322845. Epub 2011 May 17.
CD4(+)CD25(+) regulatory T (T(reg)) cells can control the allergic response to allergen, airway eosinophilia and airway hypersensitivity. We speculated that chronic inflammation persisting in asthma airways is dependent on abnormalities of these T(reg) cells. There are differences in the pathology of asthma in adults and children, and the airways of pediatric asthma are considered to be more naive than those of adults. Therefore, we analyzed the functionality of T(reg) cells in pediatric asthma and the relationship between T(reg) function and asthma symptoms.
The anergic state, which is one of the defining properties of T(reg), was analyzed by measuring intracellular Ca(2+) influx following T cell receptor (TCR) stimulation. FOXP3-positive cells and FOXP3 mRNA expression were measured by flow analysis and real-time PCR with the SYBR method, respectively.
CD45RO(+) cells make up approximately 99% of CD4(+)CD25(high) T cells and 89% of CD4(+)CD25(low) T cells in human adult blood. The proportion of CD45RO(+) cells in CD4(+)CD25(+) (high + low) T cells from pediatric asthma was much smaller (about 56%). Interestingly, our data indicated that CD45RO(+) T(reg) cells from pediatric asthma aberrantly increased intracellular Ca(2+) concentrations following TCR activation compared with pediatric nonasthma controls.
These impaired CD45RO(+) T(reg) cell functions were correlated with asthma symptoms. The correlation was observed in the group with a highly expressed atopic phenotype and longer duration of asthma. We suggest that chronic inflammation in pediatric asthma airways may be the result of impaired regulatory functions of CD45RO(+) T(reg) cells.
CD4(+)CD25(+) 调节性 T（T(reg)）细胞可以控制过敏原引起的过敏反应、气道嗜酸性粒细胞增多和气道高反应性。我们推测，哮喘气道中持续存在的慢性炎症依赖于这些 T(reg)细胞的异常。成人和儿童哮喘的病理存在差异，且儿童哮喘气道被认为比成人更幼稚。因此，我们分析了儿童哮喘 T(reg)细胞的功能以及 T(reg)功能与哮喘症状之间的关系。
通过测量 T 细胞受体（TCR）刺激后细胞内 Ca2+ 内流来分析 T(reg)的无反应状态，这是 T(reg)的定义特性之一。通过流式分析和实时 PCR 用 SYBR 法分别测量 FOXP3 阳性细胞和 FOXP3 mRNA 表达。
CD45RO(+)细胞构成人成人血液中 CD4(+)CD25(high)T 细胞的约 99%和 CD4(+)CD25(low)T 细胞的 89%。儿科哮喘患者 CD4(+)CD25(+)（高+低）T 细胞中 CD45RO(+)细胞的比例小得多（约 56%）。有趣的是，我们的数据表明，与儿科非哮喘对照相比，儿科哮喘患者的 CD45RO(+)T(reg)细胞在 TCR 激活后细胞内 Ca2+浓度异常增加。
这些受损的 CD45RO(+)T(reg)细胞功能与哮喘症状相关。在高表达特应性表型和哮喘持续时间较长的组中观察到这种相关性。我们认为，儿科哮喘气道中的慢性炎症可能是 CD45RO(+)T(reg)细胞调节功能受损的结果。
