Peripheral T Cells Re-Enter the Thymus and Interfere with Central Tolerance Induction
Peripheral T Cells Re-Enter the Thymus and Interfere with Central Tolerance Induction
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DOI：
10.4049/jimmunol.1004010
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发表时间：
2011-05-15
影响因子：
4.4
通讯作者：
Brocker, Thomas
中科院分区：
文献类型：
--
作者：
Edelmann, Stephanie L.;Marconi, Peggy;Brocker, Thomas
胸腺主要含有经过胸腺选择的发育中的胸腺细胞。此外，一些成熟的激活的外周T细胞可以重新进入胸腺。我们在这项研究中证明，过继转移的同基因抗原特异性T细胞可以进入淋巴细胞减少症小鼠的胸腺，在那里它们以抗原特异性的方式删除胸腺树突状细胞和髓质胸腺上皮细胞，而不会改变胸腺的一般功能。这诱导胸腺持续释放自身反应性自身抗原特异性T细胞，这表明过继转移激活的T细胞可以通过消除对自身特异性的负面选择而特异性地改变内源性T细胞谱系。尤其是在过继转移的T细胞引起移植物抗宿主病或移植物抗白血病的临床环境中，以及在过继的肿瘤治疗中，这些发现可能是重要的，因为内源性T细胞谱系可能偏斜，导致这两种表现。免疫学杂志，2011,186：5612-5619。
The thymus mainly contains developing thymocytes that undergo thymic selection. In addition, some mature activated peripheral T cells can re-enter the thymus. We demonstrated in this study that adoptively transferred syngeneic Ag-specific T cells can enter the thymus of lymphopenic mice, where they delete thymic dendritic cells and medullary thymic epithelial cells in an Ag-specific fashion, without altering general thymic functions. This induced sustained thymic release of autoreactive self-Ag-specific T cells suggested that adoptively transferred activated T cells can specifically alter the endogenous T cell repertoire by erasing negative selection of their own specificities. Especially in clinical settings in which adoptively transferred T cells cause graft-versus-host disease or graft-versus-leukemia, as well as in adoptive tumor therapies, these findings might be of importance, because the endogenous T cell repertoire might be skewed to contribute to both manifestations. The Journal of Immunology, 2011, 186: 5612-5619.