Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis MN 55414, USA.
Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2072-7. doi: 10.1073/pnas.1105771109. Epub 2012 Jan 23.
The ability to induce humoral and cellular immunity via antigen delivery through the unbroken skin (epicutaneous immunization, EPI) has immediate relevance for vaccine development. However, it is unclear which adjuvants induce protective memory CD8 T-cell responses by this route, and the molecular and cellular requirements for priming through intact skin are not defined. We report that cholera toxin (CT) is superior to other adjuvants in its ability to prime memory CD8 T cells that control bacterial and viral challenges. Epicutaneous immunization with CT does not require engagement of classic toll-like receptor (TLR) and inflammasome pathways and, surprisingly, is independent of skin langerin-expressing cells (including Langerhans cells). However, CT adjuvanticity required type-I IFN sensitivity, participation of a Batf3-dependent dendritic cell (DC) population and engagement of CT with suitable gangliosides. Chemoenzymatic generation of CT-antigen fusion proteins led to efficient priming of the CD8 T-cell responses, paving the way for development of this immunization strategy as a therapeutic option.
通过完整皮肤（皮内免疫，EPI）进行抗原递呈来诱导体液和细胞免疫的能力与疫苗开发直接相关。然而，目前尚不清楚哪种佐剂通过这种途径诱导保护性记忆 CD8 T 细胞反应，并且通过完整皮肤引发初始免疫的分子和细胞要求尚未确定。我们报告称，霍乱毒素（CT）在诱导控制细菌和病毒挑战的记忆 CD8 T 细胞方面优于其他佐剂。用 CT 进行皮内免疫不需要经典的 toll 样受体（TLR）和炎症小体途径的参与，而且令人惊讶的是，它不依赖于皮肤 langerin 表达细胞（包括朗格汉斯细胞）。然而，CT 的佐剂活性需要 I 型干扰素敏感性、Batf3 依赖性树突状细胞（DC）群体的参与以及 CT 与合适神经节苷脂的结合。化学酶促生成 CT-抗原融合蛋白可有效引发 CD8 T 细胞反应，为将这种免疫策略作为一种治疗选择进行开发铺平了道路。
