Directly Transfected Langerin+ Dermal Dendritic Cells Potentiate CD8+ T Cell Responses following Intradermal Plasmid DNA Immunization
Directly Transfected Langerin+ Dermal Dendritic Cells Potentiate CD8+ T Cell Responses following Intradermal Plasmid DNA Immunization
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DOI：
10.4049/jimmunol.1001825
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发表时间：
2010-09-15
影响因子：
4.4
通讯作者：
Hovav, Avi-Hai
中科院分区：
文献类型：
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作者：
Elnekave, Mazal;Furmanov, Karina;Hovav, Avi-Hai
树突状细胞（DC）在DNA疫苗接种后的CD 8（+）T细胞引发中起关键作用。与其他DNA注射途径或用病毒载体免疫相反，在将质粒DNA针注射到皮肤中后，Ag呈递被延迟。各种皮肤DC子集对该过程的贡献尚不清楚。在这项研究中，我们发现真皮CD 11 c（+）细胞是免疫后最重要的转基因表达细胞。使用兰杰林-白喉毒素受体小鼠，我们证明兰杰林（+）真皮DC（Ln（+）dDC）对于产生最佳CD 8（+）T细胞应答至关重要。阻止皮肤细胞迁移到淋巴结（LN）可以消除免疫原性，这表明dDC亚群迁移到LN对于产生免疫力至关重要。这种迁移在体内产生了弱的Ag呈递活性，直到免疫后第5天，然后急剧增加。我们进一步发现，在免疫后最初8天期间，Ln（+）dDC和dDC是唯一直接向CD 8（+）T细胞离体递呈抗原的DC群体。这种活性在随后的几天发生变化，此时皮肤DC和LN驻留DC都能够将Ag呈递给CD 8（+）T细胞。总之，我们的体内和离体结果表明，皮内质粒DNA免疫后CD 8（+）T细胞的活化依赖于直接转染的Ln（+）dDC和dDC。此外，呈递Ag的DC类型随时间而改变，Ln（+）dDC在增强初始CD 8（+）T细胞应答中起主要作用。免疫学杂志，2010，185：3463-3471。
Dendritic cells (DCs) play a critical role in CD8(+) T cell priming following DNA vaccination. In contrast to other DNA injection routes or immunization with viral vectors, Ag presentation is delayed following needle injection of plasmid DNA into the skin. The contribution of various skin DC subsets to this process is not known. In this study, we show that dermal CD11c(+) cells are the most important transgene-expressing cells following immunization. Using langerin- diphtheria toxin receptor mice we demonstrated that langerin(+) dermal DCs (Ln(+)dDCs) were crucial for generating an optimal CD8(+) T cell response. Blocking migration of skin cells to the lymph node (LN) ablated immunogenicity, suggesting that migration of dDC subsets to the LN is essential for generating immunity. This migration generated a weak Ag-presenting activity in vivo until day 5 postimmunization, which then increased dramatically. We further found that Ln(+)dDCs and dDCs were the only DC populations directly presenting Ag to CD8(+) T cells ex vivo during the initial 8-d period postimmunization. This activity changed on the following days, when both skin DCs and LN-resident DCs were able to present Ag to CD8(+) T cells. Taken together, our in vivo and ex vivo results suggest that activation of CD8(+) T cells following intradermal plasmid DNA immunization depends on directly transfected Ln(+)dDCs and dDCs. Moreover, the type of DCs presenting Ag changed over time, with Ln(+)dDCs playing the major role in potentiating the initial CD8(+) T cell response. The Journal of Immunology, 2010, 185: 3463-3471.