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

Mast 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. [Display omitted] •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 The impact of mast cells on T-cell-dominated adaptive immunity and diseases is poorly mechanistically defined. Dudeck et al. identify the distinct potential of mast-cell-derived TNF to amplify CD8+ T cell expansion and CD8+ T-cell-driven adaptive immune responses by modulating the CD8+ DC migration and priming efficiency.