Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance
Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance
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DOI：
10.1038/ni1059
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发表时间：
2004-05-01
影响因子：
30.5
通讯作者：
Pardoll, DM
中科院分区：
文献类型：
--
作者：
Yang, YP;Huang, CT;Pardoll, DM
癌症免疫治疗的一个主要障碍是肿瘤特异性T细胞耐受。在这里，我们比较了血凝素（HA）编码重组病毒与“HA负载”树突状细胞逆转HA特异性CD8耐受性和保护小鼠免受肿瘤攻击的能力。两种疫苗在激活幼稚HA特异性CD8（+）T细胞方面相当。然而，在已建立耐受性的情况下，病毒疫苗可以在CD4（+）CD25（+）调节性T细胞存在的情况下打破CD8耐受性，而树突状细胞疫苗只有在去除调节性T细胞或共同给予Toll样受体（TLR）配体或不相关病毒后才能实现这一点。这些结果表明，病毒提供了绕过调节性T细胞介导的耐受性所需的TLR信号，并强调了在建立耐受性的背景下持续TLR信号对于免疫治疗的重要性。
One chief barrier to cancer immunotherapy is tumor-specific T cell tolerance. Here we compared the ability of hemagglutinin (HA)-encoding recombinant viruses versus 'HA-loaded' dendritic cells to reverse HA-specific CD8 tolerance and to protect mice from tumor challenge. Both vaccines were comparable in activating naive HA-specific CD8(+) T cells. However, in circumstances of established tolerance, viral vaccines could break CD8 tolerance in the presence of CD4(+)CD25(+) regulatory T cells, whereas dendritic cell-based vaccines achieved this only after removal of regulatory T cells or the coadministration of a Toll-like receptor (TLR) ligand or irrelevant virus. These results demonstrate that virus provides TLR signals required for bypassing regulatory T cell-mediated tolerance and emphasize the importance of persistent TLR signals for immunotherapy in the setting of established tolerance.