Mast-Cell-Derived TNF Amplifies CD+ Dendritic Cell Functionality and CDir T Cell Priming
Mast-Cell-Derived TNF Amplifies CD+ Dendritic Cell Functionality and CDir T Cell Priming
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DOI：
10.1016/j.celrep.2015.08.078
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发表时间：
2015-10-13
期刊：
影响因子：
8.8
通讯作者：
Dudeck, Anne
中科院分区：
文献类型：
--
作者：
Dudeck, Jan;Ghouse, Shanawaz Mohammed;Dudeck, Anne
肥大细胞是接触性超敏反应模型中获得性免疫的关键启动子，但过敏原致敏的机制知之甚少。使用Mcpt 5-CreTNF（FL/FL）小鼠，我们在这里显示，在肥大细胞中TNF的缺失只损害了致敏后CD 8（+）T细胞的扩增和T细胞驱动的适应性免疫应答。在不存在肥大细胞TNF的情况下引发的T细胞表现出将致敏转移至幼稚受体的效率降低。特别是，肥大细胞TNF促进CD 8（+）树突状细胞（DC）成熟和迁移到引流淋巴结。外周释放的肥大细胞TNF进一步关键性地提高CD 8 + DC的CD 8 + T细胞引发效率，从而将肥大细胞对T细胞的作用与DC调节联系起来。总的来说，我们的研究结果确定了肥大细胞TNF放大CD 8（+）DC功能和CD 8（+）T细胞主导的适应性免疫的独特潜力，这可能对免疫治疗和疫苗接种方法非常重要。
Mast cells are critical promoters of adaptive immunity in the contact hypersensitivity model, but the mechanism of allergen sensitization is poorly understood. Using Mcpt5-CreTNF(FL/FL) mice, we show here that the absence of TNF exclusively in mast cells impaired the expansion of CD8(+) T cells upon sensitization and the T-cell-driven adaptive immune response to elicitation. T cells primed in the absence of mast cell TNF exhibited a diminished efficiency to transfer sensitization to naive recipients. Specifically, mast cell TNF promotes CD8(+) dendritic cell (DC) maturation and migration to draining lymph nodes. The peripherally released mast cell TNF further critically boosts the CD8(+) T-cell-priming efficiency of CDS' DCs, thereby linking mast cell effects on T cells to DC modulation. Collectively, our findings identify the distinct potential of mast cell TNF to amplify CD8(+) DC functionality and CD8(+) T-cell-dominated adaptive immunity, which may be of great importance for immunotherapy and vaccination approaches.