Foxp3+ T Cells Induce Perforin-Dependent Dendritic Cell Death in Tumor-Draining Lymph Nodes
Foxp3+ T Cells Induce Perforin-Dependent Dendritic Cell Death in Tumor-Draining Lymph Nodes
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DOI：
10.1016/j.immuni.2009.11.015
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发表时间：
2010-02-26
期刊：
影响因子：
32.4
通讯作者：
Amigorena, Sebastian
中科院分区：
文献类型：
--
作者：
Boissonnas, Alexandre;Scholer-Dahirel, Alix;Amigorena, Sebastian
调节性T(Treg)细胞通过尚不明确的机制限制有效的抗肿瘤免疫的开始。我们发现，表达OVA的MCA101肿瘤的排斥反应既需要OVA特异性CD8(+)T细胞受体转基因T细胞(OTI)的过继转移，也需要Foxp3(+)T细胞的中和。在肿瘤引流的淋巴结中，Foxp3(+)T细胞中和诱导OTIT细胞的迁移明显停止，树突状细胞(DC)数量增加，并增强OTIT细胞的启动。采用体外细胞毒试验和过继转移DC后的双光子显微镜观察，我们发现Foxp3(+)T细胞在肿瘤引流的淋巴结中诱导DC死亡，但在无肿瘤的情况下不能。DC死亡与Foxp3(+)T细胞-DC接触有关，且与肿瘤抗原和穿孔素相关。我们的结论是，肿瘤引流淋巴结中Foxp3(+)T细胞依赖的DC死亡限制了CD8(+)T细胞反应的开始。
Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established oval-burnin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T cell neutralization induced a marked arrest in the migration of OTI T cells, increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming. Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs in tumor-draining lymph nodes, but not in the absence of tumor. DC death correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor-draining lymph nodes limits the onset of CD8(+) T cell responses.