Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation.

Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation.
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DOI:
10.1084/jem.20092465
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发表时间:
2010-04-12
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Engelhard VH
Engelhard VH
中科院分区:
其他
文献类型:
--
作者:
Cohen JN;Guidi CJ;Tewalt EF;Qiao H;Rouhani SJ;Ruddell A;Farr AG;Tung KS;Engelhard VH

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外周免疫耐受通常被认为是由静止的组织驻留树突状细胞将组织来源的蛋白交叉呈递给逃避胸腺阴性选择的自身反应性T细胞,导致无反应性或缺失。最近,我们和其他人已经暗示淋巴结(LN)基质介导的CD8 T细胞外周耐受。我们证明,LN驻留淋巴管内皮细胞表达多种外周组织抗原(PTA)的自身免疫调节(Aire)的独立。它们直接将源自其中之一黑素细胞特异性蛋白酪氨酸酶的表位呈递给酪氨酸酶特异性CD8 T细胞,导致其缺失。我们还表明,其他LN基质亚群表达不同的PTA的机制,不同的Aire依赖。这些结果建立了淋巴管内皮细胞,和潜在的其他LN驻留细胞,作为外周免疫耐受的全身介质。
Peripheral immune tolerance is generally thought to result from cross-presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the lymph node (LN) stroma in mediating CD8 T cell peripheral tolerance. We demonstrate that LN-resident lymphatic endothelial cells express multiple peripheral tissue antigens (PTAs) independent of the autoimmune regulator (Aire). They directly present an epitope derived from one of these, the melanocyte-specific protein tyrosinase, to tyrosinase-specific CD8 T cells, leading to their deletion. We also show that other LN stromal subpopulations express distinct PTAs by mechanisms that vary in their Aire dependence. These results establish lymphatic endothelial cells, and potentially other LN-resident cells, as systemic mediators of peripheral immune tolerance.
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