title: Immune Reactions against Gene Gun Vaccines Are Differentially Modulated by Distinct Dendritic Cell Subsets in the Skin.
abstract: The skin accommodates multiple dendritic cell (DC) subsets with remarkable functional diversity. Immune reactions are initiated and modulated by the triggering of DC by pathogen-associated or endogenous danger signals. In contrast to these processes, the influence of intrinsic features of protein antigens on the strength and type of immune responses is much less understood. Therefore, we investigated the involvement of distinct DC subsets in immune reactions against two structurally different model antigens, E. coli beta-galactosidase (betaGal) and chicken ovalbumin (OVA) under otherwise identical conditions. After epicutaneous administration of the respective DNA vaccines with a gene gun, wild type mice induced robust immune responses against both antigens. However, ablation of langerin+ DC almost abolished IgG1 and cytotoxic T lymphocytes against betaGal but enhanced T cell and antibody responses against OVA. We identified epidermal Langerhans cells (LC) as the subset responsible for the suppression of anti-OVA reactions and found regulatory T cells critically involved in this process. In contrast, reactions against betaGal were not affected by the selective elimination of LC, indicating that this antigen required a different langerin+ DC subset. The opposing findings obtained with OVA and betaGal vaccines were not due to immune-modulating activities of either the plasmid DNA or the antigen gene products, nor did the differential cellular localization, size or dose of the two proteins account for the opposite effects. Thus, skin-borne protein antigens may be differentially handled by distinct DC subsets, and, in this way, intrinsic features of the antigen can participate in immune modulation.
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Corinna Stefanie
authors.initials: CS
authors.lastname: Weber
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Katrina
authors.initials: K
authors.lastname: Hainz
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Tekalign
authors.initials: T
authors.lastname: Deressa
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Helen
authors.initials: H
authors.lastname: Strandt
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Douglas
authors.initials: D
authors.lastname: Florindo Pinheiro
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mittermair
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pizarro Pesado
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria; Central Animal Laboratories, University of Salzburg, Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Hammerl
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria; Christian Doppler Laboratory for Allergy Diagnosis and Therapy, University of Salzburg, Salzburg, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Stoecklinger
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D019470:Biolistics / Q000379:methods; D002645:Chickens; D003713:Dendritic Cells / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012867:Skin / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D001616:beta-Galactosidase / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D010047:Ovalbumin; D001616:beta-Galactosidase