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首页> 外文期刊>Nature immunology >Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance.
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Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance.

机译:髓样胸腺上皮细胞在中央CD4(+)T细胞耐受性中的自主作用。

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Medullary thymic epithelial cells (mTECs) serve an essential function in central tolerance by expressing peripheral-tissue antigens. These antigens may be transferred to and presented by dendritic cells (DCs). Therefore, it is unclear whether mTECs, in addition to being an antigen reservoir, also serve a mandatory function as antigen-presenting cells. Here we diminished major histocompatibility complex (MHC) class II on mTECs through transgenic expression of a 'designer' microRNA specific for the MHC class II transactivator CIITA (called 'C2TA' here). This resulted in an enlarged polyclonal CD4(+) single-positive compartment and, among thymocytes specific for model antigens expressed in mTECs, enhanced selection of regulatory T cells (T(reg) cells) at the expense of deletion. Our data document an autonomous contribution of mTECs to both dominant and recessive mechanisms of CD4(+) T cell tolerance and support an avidity model of T(reg) cell development versus deletion.
机译:髓样胸腺上皮细胞(mTECs)通过表达外周组织抗原在中枢耐受中起重要作用。这些抗原可以转移至树突细胞(DC)并由树突细胞(DC)呈递。因此,目前尚不清楚mTECs除了是抗原库外,是否还起着强制性功能作为抗原呈递细胞。在这里,我们通过转基因表达特异于MHC II类反式激活因子CIITA的“设计者” microRNA(在此处称为“ C2TA”),减少了mTECs上的II类主要组织相容性复合物(MHC)。这导致扩大的多克隆CD4(+)单阳性区室,并且在特异性针对mTECs中表达的模型抗原的胸腺细胞中,增加了对调节性T细胞(T(reg)细胞)的选择,但以删除为代价。我们的数据记录了mTEC对CD4(+)T细胞耐受的显性和隐性机制的自主贡献,并支持T(reg)细胞发育与缺失的亲和力模型。

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