title: Efficient transduction of mature CD83+ dendritic cells using recombinant adenovirus suppressed T cell stimulatory capacity.
abstract: We have developed a culture method for the foreign serum-free generation of highly immunostimulatory, CD83+ human dendritic cells (DC). In this study, we evaluated the feasibility and consequences of endogenously expressing antigens in mature DC using adenoviral vectors. Transduction of DC with Ad-EGFP demonstrated endogenous fluorescence in 50-85% of CD83+ DC. Ad-transduced DC stimulated the proliferation of allogeneic CD8+ and CD4+ T cells at low DC: T cell ratios. However, at high DC: T cell ratios the stimulatory capacity of Ad-transduced DC was suppressed. This immunosuppressive effect was confirmed by demonstrating that the stimulatory function of untreated DC could be suppressed in a dose-dependent manner by addition of Ad-transduced DC. Furthermore, transwell experiments suggested that direct cell contact was required. Taken together, our results demonstrate the feasibility of efficiently expressing antigens in CD83+ DC using adenoviruses. However, immunosuppressive effects must be considered and carefully studied before Ad-transduced DC are employed for clinical trials. Gene Therapy (2000) 7, 249-254.
authors.affiliation: Department of Dermatology, J Gutenberg-University, Langenbeckstrasse 1, D-55101 Mainz, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Jonuleit
authors.forename: T
authors.initials: T
authors.lastname: Tüting
authors.forename: J
authors.initials: J
authors.lastname: Steitz
authors.forename: J
authors.initials: J
authors.lastname: Brück
authors.forename: A
authors.initials: A
authors.lastname: Giesecke
authors.forename: K
authors.initials: K
authors.lastname: Steinbrink
authors.forename: J
authors.initials: J
authors.lastname: Knop
authors.forename: A H
authors.initials: AH
authors.lastname: Enk
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007110:Immunity, Active; D010641:Phenotype; D014161:Transduction, Genetic / Q000235:genetics*