Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells
Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells
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DOI：
10.1038/ni1444
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发表时间：
2007-04-01
影响因子：
30.5
通讯作者：
Klein, Ludger
中科院分区：
文献类型：
--
作者：
Aschenbrenner, Katharina;D'Cruz, Louise M.;Klein, Ludger
确定自身反应性CD4（+）胸腺细胞是否被删除（隐性耐受）或分化为调节性T细胞（显性耐受）的参数尚未解决。树突状细胞直接删除胸腺细胞，部分通过交叉呈递外周抗原“混杂地”表达在对自身免疫调节因子Aire呈阳性的髓质胸腺上皮细胞（mTECs）中。目前尚不清楚mTEC本身是否以及如何在耐受诱导期间充当抗原呈递细胞。在这里，我们发现，主要组织相容性II类分子的mTECs的缺乏导致更少的多克隆调节性T细胞。此外，将模型抗原靶向Aire（+）mTEC导致特异性调节性T细胞的产生，而不依赖于抗原转移至树突细胞。因此，mTEC衍生的自身抗原的“路由”可以决定特定的胸腺细胞是否被删除或进入调节性T细胞谱系。
The parameters specifying whether autoreactive CD4(+) thymocytes are deleted ( recessive tolerance) or differentiate into regulatory T cells ( dominant tolerance) remain unresolved. Dendritic cells directly delete thymocytes, partly through cross-presentation of peripheral antigens ` promiscuously' expressed in medullary thymic epithelial cells ( mTECs) positive for the autoimmune regulator Aire. It is unclear if and how mTECs themselves act as antigen-presenting cells during tolerance induction. Here we found that an absence of major histocompatibility class II molecules on mTECs resulted in fewer polyclonal regulatory T cells. Furthermore, targeting of a model antigen to Aire(+) mTECs led to the generation of specific regulatory T cells independently of antigen transfer to dendritic cells. Thus, 'routing' of mTEC-derived self antigens may determine whether specific thymocytes are deleted or enter the regulatory T cell lineage.