title: T cell killing by tolerogenic dendritic cells protects mice from allergy.
abstract: It is well established that allergy development can be prevented by repeated low-dose exposure to contact allergens. Exactly which immune mechanisms are responsible for this so-called low zone tolerance (LZT) is not clear, although CD8⁺ suppressor T cells are known to have a role. Here, we show that TNF released by tolerogenic CD11⁺CD8⁺ DCs located in skin-draining lymph nodes is required and sufficient for development of tolerance to contact allergens in mice. DC-derived TNF protected mice from contact allergy by inducing apoptosis in allergen-specific effector CD8⁺ T cells via TNF receptor 2 but did not contribute to the generation and function of the regulatory T cells associated with LZT. The TNF-mediated killing mechanism was induced in an allergen-specific manner. Activation of tolerogenic DCs by LZT CD8⁺ suppressor T cells and enhanced TNF receptor 2 expression on contact allergen-specific CD8⁺ effector T cells were required for LZT. Our findings may explain how tolerance protects from allergic diseases, which could allow for the development of new strategies for allergy prevention.
authors: Department of Dermatology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors: Ulrike
authors: U
authors: Luckey
authors: Marcus
authors: M
authors: Maurer
authors: Talkea
authors: T
authors: Schmidt
authors: Nadine
authors: N
authors: Lorenz
authors: Beate
authors: B
authors: Seebach
authors: Martin
authors: M
authors: Metz
authors: Kerstin
authors: K
authors: Steinbrink
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000276:immunology
chemical_list: D000485:Allergens; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha