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Woodchuck dendritic cells generated from peripheral blood mononuclear cells and transduced with recombinant human adenovirus serotype 5 induce antigen-specific cellular immune responses

✍ Scribed by Laura Ochoa-Callejero; Pedro Berraondo; Julien Crettaz; Cristina Olagüe; África Vales; Juan Ruiz; Jesús Prieto; Bud C. Tennant; Stephan Menne; Gloria González-Aseguinolaza


Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
222 KB
Volume
79
Category
Article
ISSN
0146-6615

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✦ Synopsis


Abstract

Woodchucks infected with the woodchuck hepatitis virus (WHV) is the best available animal model for testing the immunotherapeutic effects of dendritic cells (DCs) in the setting of a chronic infection, as woodchucks develop a persistent infection resembling that seen in humans infected with the hepatitis B virus. In the present study, DCs were generated from woodchuck peripheral blood mononuclear cells (wDCs) in the presence of human granulocyte macrophage colony‐stimulating factor (hGM‐CSF) and human interleukin 4 (hIL‐4). After 7 days of culture, cells with morphology similar to DCs were stained positively with a cross‐reactive anti‐human CD86 antibody. Functional analysis showed that uptake of FITC‐dextran by wDCs was very efficient and was partially inhibited after LPS‐induced maturation. Furthermore, wDCs stimulated allogenic lymphocytes and induced proliferation. Moreover, wDCs were transduced efficiently with a human adenovirus serotype 5 for the expression of β‐galactosidase. Following transduction and in vivo administration of such DCs into woodchucks, an antigen‐specific cellular immune response was induced. These results demonstrate that wDCs can be generated from the peripheral blood. Following transfection with a recombinant adenovirus wDCs can be used as a feasible and effective tool for eliciting WHV‐specific T‐cell responses indicating their potential to serve as prophylactic and therapeutic vaccines. J. Med. Virol. 79:522–529, 2007. © 2007 Wiley‐Liss, Inc.