CD4+CD25+调节性T细胞在儿童哮喘发病机制中的作用初探

目的探讨哮喘急性发作患儿CD4+CD25+调节性T(Tr)细胞数量变化及影响其发育成熟的因素.方法观察20例哮喘患儿及相同数量同龄对照组.用流式细胞术检测外周血单个核细胞(PBMC)CD4、CD25表面标志及CD4+CD25+细胞内白细胞介素(IL-10)和转化生长因子受体(TGF-β)表达.用逆转录-聚合酶链反应(RT-PCR) 和荧光定量聚合酶链反应(Real-time PCR)检测PBMC Foxp3及SOCS1 mRNA表达.结果急性发作期哮喘患儿CD4+CD25+Tr细胞百分率(6.5%±1.9%)明显低于同龄对照组(12.0%±2.3%),P<0.01 ;CD4+CD25++IL-10及CD4+CD25++TGF-β分泌细胞亦明显低于对照组.Foxp3及SOCS1mRNA表达也显著降低( Foxp30.12±0.05 vs 1.71±0.58,P<0.001;SOCS10.38±0.19 vs 2.14±0.41,P<0.001).结论哮喘患儿CD4+CD25+Tr细胞明显降低可能参与哮喘发病,Foxp3及SOCS1表达降低可能是导致CD4+CD25+Tr细胞发育障碍的重要因素.

The role of CD4+ CD25+ regulatory T cells in the pathogenesis of asthma in children

OBJECTIVE: To investigate the role of CD4(+)CD25(+) regulatory T cells (Tr cells) in the pathogenesis of asthma in children. METHODS: Peripheral blood samples were collected from 20 pediatric patients with asthma, 10 male and 10 female, aged 7 (3-12), and 20 healthy children, 10 male and 10 female, aged 6.5 (2-11). Lymphocytes were isolated. Flow cytometry was used to examine the percentages of CD4(+)CD25(+) regulatory T cells, IL-10 secreting CD4(+)CD25(+) regulatory T cells (CD4(+)CD25(+)-IL-10), and transforming growth factor (TGF)-beta secreting CD4(+)CD25(+) regulatory T cells (CD4(+)CD25(+)-TGF-beta). RT-PCR and real-time PCR were used to detect the mRNA expression of suppressor of cytokine signal 1 (SOSC1) and Foxp3. RESULTS: The percentages of CD4(+)CD25(+) regulatory T cells of the asthma children was 6.51% +/- 1.94%, significantly lower than that of the healthy children (11.96% +/- 2.30%, P < 0.01); the percentage of CD4(+)CD25(+)-IL-10 of the asthma children was 1.46% +/- 0.35%, significantly lower than that of the healthy children (5.65% +/- 1.70%, P < 0.01); and the percentage of CD4(+)CD25(+)-TGF-beta of the asthma children was 1.24% +/- 0.21%, significantly lower than that t of the healthy children (4.23% +/- 1.65%, P < 0.01). The Foxp3 mRNA expression of the asthma children was 0.12 +/- 0.05, significantly lower than that of the healthy children (1.71 +/- 0.58, P < 0.01); and the SOCS1 mRNA expression of the asthma children was 0.38 +/- 0.19, significantly lower than that of the healthy children (1.51 +/- 0.41, P < 0.01). CONCLUSION: The decrease of CD4(+)CD25(+) regulatory T cells may be involved in the pathogenesis of asthma. The decreased mRNA expression of Foxp3 and SOCS1 may be associated with the aberrant development of CD4(+)CD25(+) regulatory T cells.