Mast-Cell-Derived TNF Amplifies CD8+ Dendritic Cell Functionality and CD8+ T Cell Priming
Jan Dudeck,
Shanawaz Mohammed Ghouse,
Christian H.K. Lehmann,
Anja Hoppe,
Nadja Schubert,
Sergei A. Nedospasov,
Diana Dudziak,
Anne Dudeck
Affiliations
Jan Dudeck
Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany
Shanawaz Mohammed Ghouse
Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany
Christian H.K. Lehmann
Department of Dermatology, Laboratories of DC Biology, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany
Anja Hoppe
Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany
Nadja Schubert
Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany
Sergei A. Nedospasov
Engelhardt Institute of Molecular Biology and Lomonosov Moscow State University, Moscow 119991, Russia
Diana Dudziak
Department of Dermatology, Laboratories of DC Biology, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany
Anne Dudeck
Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany
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.
