Intradermal Immunization Triggers Epidermal Langerhans Cell Mobilization Required for CD8 T-Cell Immune Responses
Intradermal Immunization Triggers Epidermal Langerhans Cell Mobilization Required for CD8 T-Cell Immune Responses
复制标题
DOI：
10.1038/jid.2011.346
复制
发表时间：
2012-03-01
影响因子：
6.5
通讯作者：
Combadiere, Behazine
中科院分区：
文献类型：
--
作者：
Liard, Christelle;Munier, Severine;Combadiere, Behazine
现在已经确定了皮肤免疫系统对产生强大的体液和细胞免疫反应的潜力。但是，在皮内（ID）疫苗接种过程中，导致皮肤抗原抗原细胞（APC）功效的机制仍有待阐明。我们先前在临床试验中已经证明了通过经皮免疫对兰格汉斯细胞（LC）的优先靶向塑造了对疫苗特异性CD8 T细胞的免疫反应。其他人则表明，靶向真皮APC的疫苗的ID接种，动员了免疫的细胞和体液臂。在这里，我们研究了表皮LCS对ID免疫的参与。当将人或小鼠皮肤注入基于粒子的疫苗ID时，我们观察到表皮LCS的形态及其动员对真皮的显着修饰。我们进一步确定，ID施用后的LC募集对于诱导抗原特异性CD8 T细胞至关重要，但是，对于特定的CD4 T细胞的产生和中和抗体是可分配的。因此，表皮和皮肤APC塑造了对ID疫苗接种的免疫反应的结果。它们的综合潜力为开发针对传染病的疫苗接种策略提供了新的途径。
The potential of the skin immune system for the generation of both powerful humoral and cellular immune responses is now well established. However, the mechanisms responsible for the efficacy of skin antigen-presenting cells (APCs) during intradermal (ID) vaccination still remain to be elucidated. We have previously demonstrated in clinical trials that preferential targeting of Langerhans cells (LCs) by transcutaneous immunization shapes the immune response toward vaccine-specific CD8 T cells. Others have shown that ID inoculation of a vaccine, which targets dermal APCs, mobilizes both the cellular and humoral arms of immunity. Here, we investigated the participation of epidermal LCs in response to ID immunization. When human or mouse skin was injected ID with a particle-based vaccine, we observed significant modifications in the morphology of epidermal LCs and their mobilization to the dermis. We further established that this LC recruitment after ID administration was essential for the induction of antigen-specific CD8 T cells, but was, however, dispensable for the generation of specific CD4 T cells and neutralizing antibodies. Thus, epidermal and dermal APCs shape the outcome of the immune responses to ID vaccination. Their combined potential provides new avenues for the development of vaccination strategies against infectious diseases.