哮喘患儿CD4+CD25+调节性T细胞的钙调节受损
2011/07/06
摘要
背景:CD4+CD25+调节性T细胞能控制针对过敏原的过敏反应、气道嗜酸性粒细胞反应和气道高反应性。我们认为,哮喘气道持续的慢性炎症取决于这些Treg细胞的异常。成人和儿童的哮喘病理学存在着差异,哮喘患儿的气道与成人相比更为稚嫩。因此,我们分析了哮喘患儿的Treg细胞功能以及Treg细胞功能与哮喘症状之间的关系。
方法:通过检测T细胞受体(TCR)刺激后的细胞内钙内流来研究过敏状态(代表了Treg细胞的特性)。FOXP3-阳性细胞和FOXP3 mRNA表达分别采用流式细胞仪和实时PCR检测。
结果:CD45RO+细胞占到成人血液的99% CD4+CD25(高)T细胞和89%的CD4+ CD25(低)T细胞。哮喘患儿CD4+CD25+ (高+低) T细胞中的CD45RO+细胞比例较低(约56%)。有意思的是,我们结果显示,哮喘患儿CD45RO+ Treg细胞在TCR活化后,与非哮喘对照相比,细胞内钙浓度异常增加。
结论:CD45RO+ Treg细胞功能受损与哮喘症状相关。该相关性见于高度表达的特异性表型和哮喘病程较长的患者。哮喘患儿气道的慢性炎症可能与CD45RO+ Treg细胞的调节功能受损有关。
(林江涛 审校)
Int Arch Allergy Immunol. 2011 May 17;156(2):148-158. [Epub ahead of print]
Impaired Ca Regulation of CD4(+)CD25(+) Regulatory T Cells from Pediatric Asthma.
Yamamoto Y, Negoro T, Hoshi A, Wakagi A, Shimizu S, Banham AH, Ishii M, Akiyama H, Kiuchi Y, Sunaga S, Tobe T, Roncador G, Itabashi K, Nakano Y.
Source
Department of Paediatrics, Tokyo Metropolitan Ebara Hospital, Tokyo, Japan.
Abstract
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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
Int Arch Allergy Immunol. 2011 May 17;156(2):148-158. [Epub ahead of print]
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哮喘的全基因组关联研究
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