Mast-Cell-Derived TNF Amplifies CD8+ Dendritic Cell Functionality and CD8+ T Cell Priming

• TNF release by mast cells is required for efficient CD8+ T cell responses to haptens
• Mast cell TNF promotes the migration and maturation of CD8+ DCs specifically
• Mast cell TNF distinctly boosts the CD8+ T-cell-priming efficiency of CD8+ DCs

SummaryMast cells are critical promoters of adaptive immunity in the contact hypersensitivity model, but the mechanism of allergen sensitization is poorly understood. Using Mcpt5-CreTNFFL/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 CD8+ 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.

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