Conventional Dendritic Cells Are Required for the Activation of Helper-Dependent CD8 T Cell Responses to a Model Antigen After Cutaneous Vaccination with Lentiviral Vectors
Conventional Dendritic Cells Are Required for the Activation of Helper-Dependent CD8 T Cell Responses to a Model Antigen After Cutaneous Vaccination with Lentiviral Vectors
复制标题
DOI：
10.4049/jimmunol.1002529
复制
发表时间：
2011-04-15
影响因子：
4.4
通讯作者：
Bennett, Clare L.
中科院分区：
文献类型：
--
作者：
Goold, Hugh D.;Escors, David;Bennett, Clare L.
用慢病毒载体的皮肤接种产生系统性CD 8 T细胞应答，其具有根除肿瘤用于癌症免疫治疗的潜力。然而，虽然S。尽管用< 1百万个慢病毒颗粒免疫清楚地引发细胞毒性T细胞，但用高得多的剂量接种已常规用于定义慢病毒载体激活T细胞的机制。特别地，测试树突状细胞（DC）呈递慢病毒Ag的实验需要注射高病毒滴度，这可能导致不同DC群体的异常转导。我们利用DC耗竭的可诱导小鼠模型来研究在s.c.用低剂量的慢病毒颗粒免疫。在这篇文章中，我们证明了传统的DC需要在引流淋巴结中向CD 8 T细胞呈递Ag。朗格汉斯细胞不需要激活效应子应答，朗格汉斯细胞和浆细胞样DC都不足以引发Ag特异性T细胞。免疫驱动内源性长寿命记忆T细胞的产生，这些细胞可以在没有炎症激发的情况下被重新激活以杀死Ag特异性靶标。此外，慢病毒疫苗接种激活了内源性CD 4 Th细胞的扩增，这是产生产生IFN-γ和杀死Ag特异性靶标的效应CD 8 T细胞所需的。总的来说，我们证明，皮肤免疫后，慢病毒颗粒，CD 4许可的淋巴结常规DC目前的Ag到CD 8 T细胞，导致产生的保护性内源性抗肿瘤免疫，可能是有效的癌症免疫治疗。免疫学杂志，2011，186：4565-4572。
Cutaneous vaccination with lentiviral vectors generates systemic CD8 T cell responses that have the potential to eradicate tumors for cancer immunotherapy. However, although s.c. immunization with < 1 million lentiviral particles clearly primes cytotoxic T cells, vaccination with much higher doses has routinely been used to define the mechanisms of T cell activation by lentiviral vectors. In particular, experiments to test presentation of lentiviral Ags by dendritic cells (DC) require injection of high viral titers, which may result in aberrant transduction of different DC populations. We exploited inducible murine models of DC depletion to investigate which DC prime the lentiviral response after s.c. immunization with low doses of lentiviral particles. In this article, we demonstrate that conventional DC are required to present Ag to CD8 T cells in draining lymph nodes. Langerhans cells are not required to activate the effector response, and neither Langerhans cells nor plasmacytoid DC are sufficient to prime Ag-specific T cells. Immunization drives the generation of endogenous long-lived memory T cells that can be reactivated to kill Ag-specific targets in the absence of inflammatory challenge. Furthermore, lentiviral vaccination activates expansion of endogenous CD4 Th cells, which are required for the generation of effector CD8 T cells that produce IFN-gamma and kill Ag-specific targets. Collectively, we demonstrate that after cutaneous immunization with lentiviral particles, CD4-licensed lymph node conventional DC present Ag to CD8 T cells, resulting in the generation of protective endogenous antitumor immunity that may be effective for cancer immunotherapy. The Journal of Immunology, 2011, 186: 4565-4572.