title: Mast-Cell-Derived TNF Amplifies CD8(+) Dendritic Cell Functionality and CD8(+) T Cell Priming.
abstract: 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.
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dudeck
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Shanawaz Mohammed
authors.initials: SM
authors.lastname: Ghouse
authors.affiliation: Department of Dermatology, Laboratories of DC Biology, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Christian H K
authors.initials: CH
authors.lastname: Lehmann
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Hoppe
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Schubert
authors.affiliation: Engelhardt Institute of Molecular Biology and Lomonosov Moscow State University, Moscow 119991, Russia; German Rheumatism Research Centre, a Leibniz Institute, Berlin 10117, Germany.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Nedospasov
authors.affiliation: Department of Dermatology, Laboratories of DC Biology, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Dudziak
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany. Electronic address: anne.dudeck@tu-dresden.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Dudeck
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D045142:Cross-Priming; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha