Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ T cell responses.
Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ T cell responses.
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DOI：
10.4049/jimmunol.1004120
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发表时间：
2012-03-01
期刊：
影响因子：
--
通讯作者：
Romani N
中科院分区：
文献类型：
--
作者：
Flacher V;Tripp CH;Haid B;Kissenpfennig A;Malissen B;Stoitzner P;Idoyaga J;Romani N
当抗原通过单克隆抗体（mAb）靶向内吞受体时，树突状细胞（DC）的抗原掺入增加。我们先前已经在小鼠中证明，皮内施用的抗C型凝集素的mAb被表皮朗格汉斯细胞（LC）、真皮朗格林阴性DC和真皮朗格林+DC原位摄取。然而，这些皮肤DC亚群对抗原靶向后诱导免疫应答的相对贡献尚未在体内得到解决。我们在这里表明，小鼠表皮LC和真皮DC运输皮内注射的单克隆抗体对凝集素受体DEC-205/CD 205在体内。mAb原位靶向的皮肤DC在稳态和炎症状态下通过淋巴管迁移。在皮肤引流淋巴结中，在驻留的CD 8 α+ DC和迁移的皮肤DC中发现靶向mAb。超过70%的靶向DC表达Langerin，包括真皮Langerin+ DC和LC。当皮肤被TLR 7激动剂咪喹莫特局部发炎时，淋巴结中靶向皮肤DC的数量增加2-3倍。完全去除注射卵白蛋白偶联的抗DEC-205的位点使针对加载卵白蛋白肽的靶细胞的内源性细胞毒性应答降低40- 50%。令人惊讶的是，选择性消融朗格林-白喉毒素-受体敲入小鼠中的所有朗格林+皮肤DC不影响这种应答，与所选择的佐剂无关。因此，在抗原靶向DC的皮肤免疫策略中，Langerin+皮肤DC在抗DEC-205 mAb的转运中起主要作用，尽管Langerinneg真皮DC和CD 8 α+ DC足以用于随后的CD 8 + T细胞应答。
Incorporation of antigens by dendritic cells (DCs) increases when antigens are targeted to endocytic receptors by monoclonal antibodies (mAb). We have previously demonstrated in the mouse that mAb against C-type lectins administered intradermally are taken up by epidermal Langerhans cells (LCs), dermal Langerinneg DCs and dermal Langerin+ DCs in situ. However, the relative contribution of these skin DC subsets to the induction of immune responses after antigen targeting has not been addressed in vivo. We show here that murine epidermal LCs and dermal DCs transport intradermally injected mAb against the lectin receptor DEC-205/CD205 in vivo. Skin DCs targeted in situ with mAb migrated through lymphatic vessels in steady state and inflammation. In the skin-draining lymph nodes, targeting mAb were found in resident CD8α+ DCs and in migrating skin DCs. More than 70% of targeted DCs expressed Langerin, including dermal Langerin+ DCs and LCs. Numbers of targeted skin DCs in the nodes increased 2-3-fold when skin was topically inflamed by the TLR7 agonist imiquimod. Complete removal of the site where ovalbumin-coupled anti-DEC-205 had been injected decreased endogenous cytotoxic responses against ovalbumin peptide-loaded target cells by 40-50%. Surprisingly, selective ablation of all Langerin+ skin DCs in Langerin-Diphtheria-Toxin-Receptor knock-in mice did not affect such responses, independent of the adjuvant chosen. Thus, in cutaneous immunization strategies where antigen is targeted to DCs, Langerin+ skin DCs play a major role in transport of anti-DEC-205 mAb, although Langerinneg dermal DCs and CD8α+ DCs are sufficient to subsequent CD8+ T cell responses.
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