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

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

Author information

1
Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
2
Department of Dermatology, Laboratories of DC Biology, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
3
Engelhardt Institute of Molecular Biology and Lomonosov Moscow State University, Moscow 119991, Russia; German Rheumatism Research Centre, a Leibniz Institute, Berlin 10117, Germany.
4
Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany. Electronic address: anne.dudeck@tu-dresden.de.

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.

PMID:
26411682
DOI:
10.1016/j.celrep.2015.08.078
[Indexed for MEDLINE]
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