Deletional Tolerance Mediated by Extrathymic Aire-Expressing Cells

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 naive 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. A genetic modification design type is where an organism(s) has had genetic material removed, rearranged, mutagenized or added, such as knock out. Keywords: genetic_modification_design 8 samples

自身免疫的预防需要在自身反应性T细胞的发育与成熟过程中将其清除。胸腺基质细胞表达多样的自身抗原是该过程的核心要件，这在一定程度上依赖于自身免疫调节因子（Autoimmune Regulator, Aire）基因的调控活性。本文报道了驻留于次级淋巴器官内的胸腺外表达Aire的细胞（extrathymic Aire-expressing cells, eTACs）的鉴定成果。这类源自基质的eTACs可表达多种独特的自身抗原，能够与初始自身反应性T细胞发生相互作用并将其清除。借助双光子显微镜（two-photon microscopy），我们观测到eTACs与自身反应性T细胞之间存在稳定的抗原特异性相互作用。我们认为，这类表达自身抗原的基质细胞次级网络，可通过阻断逃逸胸腺阴性选择的自身反应性T细胞的成熟进程，助力强化机体的免疫耐受。基因修饰设计类型指对生物体进行遗传物质移除、重排、诱变或添加的操作（例如敲除（knock out））。关键词：genetic_modification_design，样本量为8。