Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
J Invest Dermatol. 2010 Mar;130(3):755-62. doi: 10.1038/jid.2009.343. Epub 2009 Nov 5.
Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.
抗原提呈细胞可以捕获沉积在皮肤中的抗原，包括皮下给予的疫苗。这些包括不同的树突状细胞（DCs），如表皮朗格汉斯细胞（LCs）、真皮 DCs 和真皮 langerin+ DCs。为了评估真皮抗原进入皮肤 DCs 的情况，我们使用了针对两种 C 型凝集素内吞受体 DEC-205/CD205 和 langerin/CD207 的 mAb。当应用于鼠和人皮肤外植体培养物时，这些 mAb 被表皮 LCs 有效摄取。此外，抗 DEC-205 靶向 langerin+ CD103+ 和 langerin- CD103- 小鼠真皮 DCs。出乎意料的是，真皮内注射这两种 mAb（但不是同种型对照）导致原位 LC 强烈而快速的标记，这意味着大分子可以通过基底膜扩散到表皮。在体内用卵清蛋白偶联的抗 DEC-205 靶向的表皮 LCs 强烈地向体外的 CD4+ 和 CD8+ T 细胞呈递抗原。然而，令我们惊讶的是，通过 langerin 靶向的 LCs 无法触发 T 细胞增殖。因此，表皮 LCs 在标准疫苗接种条件下摄取结合凝集素的抗体具有重要功能。
