Mast-Cell-Derived TNF Amplifies CD+ Dendritic Cell Functionality and CDir T Cell Priming

作者：Dudeck Jan; Ghouse Shanawaz Mohammed; Lehmann Christian H K; Hoppe Anja; Schubert Nadja; Nedospasov Sergei A; Dudziak Diana; Dudeck Anne

来源：Cell Reports, 2015, 13(2): 399-411.

DOI：10.1016/j.celrep.2015.08.078

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.

• 出版日期2015-10-13