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

Autor: Jan Dudeck, Shanawaz Mohammed Ghouse, Christian H.K. Lehmann, Anja Hoppe, Nadja Schubert, Sergei A. Nedospasov, Diana Dudziak, Anne Dudeck
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Cell Reports, Vol 13, Iss 2, Pp 399-411 (2015)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2015.08.078
Popis: 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.
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