Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent.
Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent.
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CD4+ CD25+调节T细胞体内转移后气道炎症和过度反应性的分辨率取决于白介素10。
DOI：
10.1084/jem.20051166
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发表时间：
2005-12-05
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在过敏性疾病患者中观察到CD 4 + CD 25+调节性T细胞对过敏原的T细胞应答的抑制不足。我们目前的实验使用小鼠气道炎症模型来检查过敏原特异性CD 4 + CD 25 + T细胞在体内的抑制活性。将卵清蛋白（OVA）肽特异性CD 4 + CD 25 + T细胞转移至OVA致敏小鼠，可降低过敏原激发后肺中的气道高反应性（AHR）、嗜酸性粒细胞募集和辅助性T细胞2型（Th 2）细胞因子表达。这种抑制依赖于白细胞介素（IL）10，因为在转移CD 4 + CD 25 + T细胞后检测到IL-10的肺表达增加，并且抗IL-10 R抗体逆转了调节。然而，当转移来自IL-10基因缺陷小鼠的CD 4 + CD 25 + T细胞时，仍然观察到AHR抑制、气道炎症和IL-10表达增加。细胞内细胞因子染色证实，CD 4 + CD 25 + T细胞的转移诱导受体CD 4 + T细胞中的IL-10表达，但在气道巨噬细胞、树突状细胞或B细胞中未检测到IL-10表达的增加。这些数据表明，CD 4 + CD 25 + T细胞可以通过IL-10依赖性机制在体内抑制Th 2细胞驱动的对过敏原的应答，但这种抑制不需要调节性T细胞自身产生IL-10。
Deficient suppression of T cell responses to allergen by CD4+CD25+ regulatory T cells has been observed in patients with allergic disease. Our current experiments used a mouse model of airway inflammation to examine the suppressive activity of allergen-specific CD4+CD25+ T cells in vivo. Transfer of ovalbumin (OVA) peptide–specific CD4+CD25+ T cells to OVA-sensitized mice reduced airway hyperreactivity (AHR), recruitment of eosinophils, and T helper type 2 (Th2) cytokine expression in the lung after allergen challenge. This suppression was dependent on interleukin (IL) 10 because increased lung expression of IL-10 was detected after transfer of CD4+CD25+ T cells, and regulation was reversed by anti–IL-10R antibody. However, suppression of AHR, airway inflammation, and increased expression of IL-10 were still observed when CD4+CD25+ T cells from IL-10 gene–deficient mice were transferred. Intracellular cytokine staining confirmed that transfer of CD4+CD25+ T cells induced IL-10 expression in recipient CD4+ T cells, but no increase in IL-10 expression was detected in airway macrophages, dendritic cells, or B cells. These data suggest that CD4+CD25+ T cells can suppress the Th2 cell–driven response to allergen in vivo by an IL-10–dependent mechanism but that IL-10 production by the regulatory T cells themselves is not required for such suppression.