Deletional tolerance mediated by extrathymic Aire-expressing cells.

Deletional tolerance mediated by extrathymic Aire-expressing cells.
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DOI:
10.1126/science.1159407
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发表时间:
2008-08-08
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Anderson MS
Anderson MS
中科院分区:
其他
文献类型:
--
作者:
Gardner JM;Devoss JJ;Friedman RS;Wong DJ;Tan YX;Zhou X;Johannes KP;Su MA;Chang HY;Krummel MF;Anderson MS

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自身免疫的预防需要在自身反应性T细胞的发育和成熟过程中消除它们。胸腺中基质细胞表达不同的自身抗原对这一过程至关重要,并且部分取决于自身免疫调节因子(Aire)基因的活性。在这里,我们报告的鉴定胸腺外Aire表达细胞(eTAC)内的次级淋巴器官居民。这些间质来源的eTAC表达多种独特的自身抗原,并且能够与幼稚自身反应性T细胞相互作用并使其缺失。使用双光子显微镜,我们观察到eTAC和自身反应性T细胞之间稳定的抗原特异性相互作用。我们认为,这种表达自身抗原的基质细胞的次级网络可能有助于通过阻止逃避胸腺阴性选择的自身反应性T细胞的成熟来增强免疫耐受。
The prevention of autoimmunity requires elimination of self-reactive T cells during their development and maturation. Expression of diverse self-antigens by stromal cells in the thymus is essential to this process, and depends, in part, on the activity of the Autoimmune Regulator (Aire) gene. Here we report the identification of extrathymic Aire-expressing cells (eTACs) resident within the secondary lymphoid organs. These stromally-derived eTACs express a diverse array of unique self-antigens and are capable of interacting with and deleting naïve autoreactive T cells. Using two-photon microscopy we observe stable, antigen-specific interactions between eTACs and autoreactive T cells. We propose that such a secondary network of self-antigen-expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection.
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