No requirement for TRAIL in intrathymic negative selection
No requirement for TRAIL in intrathymic negative selection
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DOI：
10.1093/intimm/dxm144
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发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Smyth, Mark J.
中科院分区：
文献类型：
--
作者：
Cretney, Erika;Uldrich, Adam P.;Smyth, Mark J.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）途径对胸腺内阴性选择的贡献是一个有争议的问题，有两项研究表明TRAIL的关键作用，而其他研究则证明了TRAIL和TRAIL受体缺陷小鼠中的正常阴性选择。这些差异的基础尚不清楚，可能部分反映了正在调查的负选择模型的差异。考虑到负选择过程在建立一个有能力的免疫系统中的重要性，必须充分解决这些差异。在这项研究中，我们未能确定TRAIL在急性模型中的肽抗原特异性阴性选择使用TCR转基因系统，以及抗体介导的TCR/CD 3连接在体外和体内的作用。此外，胸腺树突状细胞，在胸腺中的负选择的主要细胞介质，不组成性表达TRAIL，和TRAIL受体（DR 5）的表达是阴性或极低的胸腺细胞。此外，体外胸腺细胞缺失在C57 BL/6 TRAIL（-/-）gld小鼠中是正常的，表明TRAIL和FasL不协同作用以诱导负选择。这些结果，结合老年C57 BL/6 TRAIL（-/-）小鼠未显示自发性自身免疫迹象的事实，强烈表明胸腺内阴性选择在没有TRAIL信号传导的情况下正常发生。
The contribution of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway to intrathymic negative selection is a controversial subject with two studies suggesting a key role for TRAIL, while others demonstrated normal negative selection, in TRAIL- and TRAIL receptor-deficient mice. The basis of these discrepancies is unclear and may in part reflect differences in the negative selection models under investigation. Considering the importance of the negative selection process in the establishment of a competent immune system, it is essential that these discrepancies be fully resolved. In this study, we failed to identify a role for TRAIL in an acute model of peptide antigen-specific negative selection using a TCR transgenic system as well as antibody-mediated TCR/CD3 ligation in vitro and in vivo. Moreover, thymic dendritic cells, the main cellular mediators of negative selection in the thymus, did not constitutively express TRAIL, and TRAIL receptor (DR5) expression was negative or extremely low on thymocytes. Furthermore, in vitro thymocyte deletion was normal in C57BL/6 TRAIL(-/-) gld mice, suggesting that TRAIL and FasL do not function cooperatively to induce negative selection. These results, combined with the fact that aged C57BL/6 TRAIL(-/-) mice showed no signs of spontaneous autoimmunity, strongly indicate that intrathymic negative selection occurs normally in the absence of TRAIL signaling.