Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance
Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance
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DOI：
10.1182/blood-2010-06-286393
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发表时间：
2011-09-01
期刊：
影响因子：
20.3
通讯作者：
Heath, William R.
中科院分区：
文献类型：
--
作者：
Hubert, Francois-Xavier;Kinkel, Sarah A.;Heath, William R.
为了研究Aire在胸腺选择中的作用，我们研究了在大鼠胰岛素启动子的控制下，表达OVA的小鼠产生卵白蛋白（OVA）特异性CD4和CD8 T细胞的细胞需求。Aire缺乏减少胸腺中成熟的单阳性OVA特异性CD4（+）或CD8(+) T细胞的数量，而不依赖于OVA的表达。重要的是，根据t细胞类型，它还以两种方式促成ova依赖性阴性选择。空气依赖性OVA特异性CD8 T细胞的负选择与空气调节的OVA表达相关。相比之下，对于OVA特异性CD4 T细胞，Aire通过一种独立于OVA表达水平的机制影响耐受诱导，控制抗原提呈细胞进入髓样胸腺上皮细胞（mTEC）表达的OVA。这项研究支持
To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter. Aire deficiency reduced the number of mature single-positive OVA-specific CD4(+) or CD8(+) T cells in the thymus, independent of OVA expression. Importantly, it also contributed in 2 ways to OVA-dependent negative selection depending on the T-cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to medullary thymic epithelial cell (mTEC)-expressed OVA. This study supports the