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

Cell Rep. 2015 Oct 13;13(2):399-411. doi: 10.1016/j.celrep.2015.08.078. Epub 2015 Sep 24.


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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cross-Priming*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Mast Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Tumor Necrosis Factor-alpha