Responses of CD4+CD25+Foxp3+ and IL-10-secreting type I T regulatory cells to cluster-specific immunotherapy for allergic rhinitis in children
Responses of CD4+CD25+Foxp3+ and IL-10-secreting type I T regulatory cells to cluster-specific immunotherapy for allergic rhinitis in children
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DOI：
10.1111/j.1399-3038.2011.01249.x
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发表时间：
2012-03-01
影响因子：
4.4
通讯作者：
Zhang, Luo
中科院分区：
文献类型：
--
作者：
Lou, Wei;Wang, Chengshuo;Zhang, Luo
我们研究了屋尘螨（Dermatophagoides pteronyssinus，Der p）的簇特异性免疫治疗（cluster specific immunotherapy，SIT）对Der p致敏的变应性鼻炎（allergic rhinitis，AR）患儿CD 4 + CD 25 + Foxp 3 + Treg细胞和IL-10分泌型T调节细胞（IL-10-secreting type I T regulatory，Tr 1）的影响。我们进行了一项前瞻性随机研究，涉及46名儿童（年龄813岁），其中25名儿童接受Der p-SIT +药物治疗，21名仅接受药物治疗，为期1年。治疗前和治疗结束时，检测CD 4 + CD 25 + Foxp 3 + Treg细胞和过敏原特异性IL-10+IL-4-、IFN-？+ IL-4-和IL-4+IFN-？-通过流式细胞术测量CD 4 + T细胞。类似地，IL-4、IFN-？、采用ELISA法检测过敏原刺激的外周血单个核细胞（PBMC）培养上清中IL-10和IL-10水平，并观察CD 4 + CD 25 high T细胞对两组PBMC增殖和细胞因子释放的抑制作用。过敏原特异性血清IgE和IgG 4也分别在治疗开始和结束时通过RAST和ELISA进行评估。与基线水平相比，SIT 1年后，来自PBMC培养物的变应原特异性Tr 1细胞、IgG 4和变应原诱导的IL-10合成水平显著增加（所有p < 0.001），Tr 1细胞水平增加与鼻部症状改善之间存在显著相关性（r = 0.48，p < 0.05）。相反，CD 4 + CD 25 + Foxp 3 + T细胞、过敏原特异性Th 1和Th 2细胞、IL-4和IFN-γ的产生水平，治疗结束时，两组CD 4 + CD 25 high T细胞功能无明显改变。这些数据表明，Tr 1细胞的上调可能在SIT中起重要作用，并且是AR患者成功SIT的有用标志物。
We investigated the effects of cluster specific immunotherapy (SIT) with Dermatophagoides pteronyssinus (Der p) on CD4+CD25+Foxp3+ Treg cells and IL-10-secreting type I T regulatory (Tr1) cells in Der p-sensitized children with allergic rhinitis (AR). We performed a prospective randomized study involving 46 children (aged 813 yr), of whom 25 children received Der p-SIT + pharmacotherapy and 21 received only pharmacotherapy, over a period of 1 yr. Prior to and at end of treatment, CD4+CD25+Foxp3+ Treg cells and allergen-specific IL-10+IL-4-, IFN-?+IL-4-, and IL-4+IFN-?-CD4+ T cells were measured by flow cytometry. Similarly, IL-4, IFN-?, and IL-10 in supernatants from allergen-stimulated peripheral blood mononuclear cell (PBMC) cultures were measured by ELISA, and the suppressive effect of CD4+CD25high T cells on cell proliferation and cytokine release was estimated from both groups. Allergen-specific serum IgE and IgG4 were also assessed at the beginning and end of treatment by RAST and ELISA, respectively. The levels of allergen-specific Tr1 cells, IgG4, and allergen-induced IL-10 synthesis from PBMC cultures were significantly increased after SIT for 1 yr compared with baseline levels (p < 0.001 for all), with significant correlation between increased levels of Tr1 cells and improvements in nasal symptoms (r = 0.48, p < 0.05). In contrast, the levels of CD4+CD25+Foxp3+ T cells, allergen-specific Th1 and Th2 cells, the production of IL-4 and IFN-?, and the function of CD4+CD25high T cells were not altered in either group at the end of treatment. These data suggest that the up-regulation of Tr1 cells may play an important role in SIT and be a useful marker of successful SIT in AR patients.