Efficient transduction of mature CD83+ dendritic cells using recombinant adenovirus suppressed T cell stimulatory capacity

被引:49
作者
Jonuleit, H [1 ]
Tüting, T [1 ]
Steitz, J [1 ]
Brück, J [1 ]
Giesecke, A [1 ]
Steinbrink, K [1 ]
Knop, J [1 ]
Enk, AH [1 ]
机构
[1] Univ Mainz, Dept Dermatol, D-55101 Mainz, Germany
关键词
dendritic cells; genetic immunization; recombinant adenovirus;
D O I
10.1038/sj.gt.3301077
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:249 / 254
页数:6
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