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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2009

Open Access 01-12-2009 | Research

Highly efficient transduction of human plasmacytoid dendritic cells without phenotypic and functional maturation

Authors: Philippe Veron, Sylvie Boutin, Samia Martin, Laurence Chaperot, Joel Plumas, Jean Davoust, Carole Masurier

Published in: Journal of Translational Medicine | Issue 1/2009

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Abstract

Background

Gene modified dendritic cells (DC) are able to modulate DC functions and induce therapeutic immunity or tolerance in an antigen-specific manner. Among the different DC subsets, plasmacytoid DC (pDC) are well known for their ability to recognize and respond to a variety of viruses by secreting high levels of type I interferon.

Methods

We analyzed here, the transduction efficiency of a pDC cell line, GEN2.2, and of pDC derived from CD34+ progenitors, using lentiviral vectors (LV) pseudotyped with different envelope glycoproteins such as the vesicular stomatitis virus envelope (VSVG), the gibbon ape leukaemia virus envelope (GaLV) or the feline endogenous virus envelope (RD114). At the same time, we evaluated transgene expression (E-GFP reporter gene) under the control of different promoters.

Results

We found that efficient gene transfer into pDC can be achieved with VSVG-pseudotyped lentiviral vectors (LV) under the control of phoshoglycerate kinase (PGK) and elongation factor-1 (EF1α) promoters (28% to 90% of E-GFP+ cells, respectively) in the absence of phenotypic and functional maturation. Surprisingly, promoters (desmin or synthetic C5–12) described as muscle-specific and which drive gene expression in single strand AAV vectors in gene therapy protocols were very highly active in pDC using VSVG-LV.

Conclusion

Taken together, our results indicate that LV vectors can serve to design pDC-based vaccines in humans, and they are also useful in vitro to evaluate the immunogenicity of the vector preparations, and the specificity and safety of given promoters used in gene therapy protocols.
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Literature
1.
Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature. 1998, 392: 245-252. 10.1038/32588.CrossRefPubMed
2.
Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol. 2000, 18: 767-811. 10.1146/annurev.immunol.18.1.767.CrossRefPubMed
3.
Pulendran B: Modulating vaccine responses with dendritic cells and Toll-like receptors. Immunol Rev. 2004, 199: 227-250. 10.1111/j.0105-2896.2004.00144.x.CrossRefPubMed
4.
Blom B, Ho S, Antonenko S, Liu YJ: Generation of interferon alpha-producing predendritic cell (Pre-DC)2 from human CD34(+) hematopoietic stem cells. J Exp Med. 2000, 192: 1785-1796. 10.1084/jem.192.12.1785.PubMedCentralCrossRefPubMed
5.
Shortman K, Liu YJ: Mouse and human dendritic cell subtypes. Nat Rev Immunol. 2002, 2: 151-161. 10.1038/nri746.CrossRefPubMed
6.
Colonna M, Trinchieri G, Liu YJ: Plasmacytoid dendritic cells in immunity. Nat Immunol. 2004, 5: 1219-1226. 10.1038/ni1141.CrossRefPubMed
7.
Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A: Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med. 2003, 198: 513-520. 10.1084/jem.20030162.PubMedCentralCrossRefPubMed
8.
Hochrein H, Schlatter B, O'Keeffe M, Wagner C, Schmitz F, Schiemann M, Bauer S, Suter M, Wagner H: Herpes simplex virus type-1 induces IFN-alpha production via Toll-like receptor 9-dependent and -independent pathways. Proc Natl Acad Sci USA. 2004, 101: 11416-11421. 10.1073/pnas.0403555101.PubMedCentralCrossRefPubMed
9.
Krug A, Luker GD, Barchet W, Leib DA, Akira S, Colonna M: Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood. 2004, 103: 1433-1437. 10.1182/blood-2003-08-2674.CrossRefPubMed
10.
Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J: Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci USA. 2004, 101: 3516-3521. 10.1073/pnas.0400525101.PubMedCentralCrossRefPubMed
11.
Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C: Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004, 303: 1529-1531. 10.1126/science.1093616.CrossRefPubMed
12.
Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S: Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 2004, 303: 1526-1529. 10.1126/science.1093620.CrossRefPubMed
13.
Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA: Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA. 2004, 101: 5598-5603. 10.1073/pnas.0400937101.PubMedCentralCrossRefPubMed
14.
Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, Colonna M: Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med. 1999, 5: 919-923. 10.1038/11360.CrossRefPubMed
15.
Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, Ho S, Antonenko S, Liu YJ: The nature of the principal type 1 interferon-producing cells in human blood. Science. 1999, 284: 1835-1837. 10.1126/science.284.5421.1835.CrossRefPubMed
16.
Liu YJ: IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol. 2005, 23: 275-306. 10.1146/annurev.immunol.23.021704.115633.CrossRefPubMed
17.
Olivier A, Lauret E, Gonin P, Galy A: The Notch ligand delta-1 is a hematopoietic development cofactor for plasmacytoid dendritic cells. Blood. 2006, 107: 2694-2701. 10.1182/blood-2005-03-0970.CrossRefPubMed
18.
Chaperot L, Blum A, Manches O, Lui G, Angel J, Molens JP, Plumas J: Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells. J Immunol. 2006, 176: 248-255.CrossRefPubMed
19.
Angel J, Chaperot L, Molens JP, Mezin P, Amacker M, Zurbriggen R, Grichine A, Plumas J: Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells. Vaccine. 2007, 25: 3913-3921. 10.1016/j.vaccine.2007.01.101.CrossRefPubMed
20.
Jaraquemada D, Marti M, Long EO: An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells. J Exp Med. 1990, 172: 947-954. 10.1084/jem.172.3.947.CrossRefPubMed
21.
Chinnasamy N, Chinnasamy D, Toso JF, Lapointe R, Candotti F, Morgan RA, Hwu P: Efficient gene transfer to human peripheral blood monocyte-derived dendritic cells using human immunodeficiency virus type 1-based lentiviral vectors. Hum Gene Ther. 2000, 11: 1901-1909. 10.1089/10430340050129512.CrossRefPubMed
22.
Schroers R, Sinha I, Segall H, Schmidt-Wolf IG, Rooney CM, Brenner MK, Sutton RE, Chen SY: Transduction of human PBMC-derived dendritic cells and macrophages by an HIV-1-based lentiviral vector system. Mol Ther. 2000, 1: 171-179. 10.1006/mthe.2000.0027.CrossRefPubMed
23.
Salmon P, Arrighi JF, Piguet V, Chapuis B, Zubler RH, Trono D, Kindler V: Transduction of CD34+ cells with lentiviral vectors enables the production of large quantities of transgene-expressing immature and mature dendritic cells. J Gene Med. 2001, 3: 311-320. 10.1002/1521-2254(200107/08)3:4<311::AID-JGM198>3.0.CO;2-B.CrossRefPubMed
24.
Rouas R, Uch R, Cleuter Y, Jordier F, Bagnis C, Mannoni P, Lewalle P, Martiat P, Broeke Van den A: Lentiviral-mediated gene delivery in human monocyte-derived dendritic cells: optimized design and procedures for highly efficient transduction compatible with clinical constraints. Cancer Gene Ther. 2002, 9: 715-724. 10.1038/sj.cgt.7700500.CrossRefPubMed
25.
Breckpot K, Dullaers M, Bonehill A, van Meirvenne S, Heirman C, de Greef C, Bruggen van der P, Thielemans K: Lentivirally transduced dendritic cells as a tool for cancer immunotherapy. J Gene Med. 2003, 5: 654-667. 10.1002/jgm.400.CrossRefPubMed
26.
Veron P, Boutin S, Bernard J, Danos O, Davoust J, Masurier C: Efficient transduction of monocyte- and CD34(+)- derived Langerhans cells with lentiviral vectors in the absence of phenotypic and functional maturation. J Gene Med. 2006, 8: 951-961. 10.1002/jgm.923.CrossRefPubMed
27.
Dyall J, Latouche JB, Schnell S, Sadelain M: Lentivirus-transduced human monocyte-derived dendritic cells efficiently stimulate antigen-specific cytotoxic T lymphocytes. Blood. 2001, 97: 114-121. 10.1182/blood.V97.1.114.CrossRefPubMed
28.
Reiser J: Production and concentration of pseudotyped HIV-1-based gene transfer vectors. Gene Ther. 2000, 7: 910-913. 10.1038/sj.gt.3301188.CrossRefPubMed
29.
Stitz J, Buchholz CJ, Engelstadter M, Uckert W, Bloemer U, Schmitt I, Cichutek K: Lentiviral vectors pseudotyped with envelope glycoproteins derived from gibbon ape leukemia virus and murine leukemia virus 10A1. Virology. 2000, 273: 16-20. 10.1006/viro.2000.0394.CrossRefPubMed
30.
Hanawa H, Kelly PF, Nathwani AC, Persons DA, Vandergriff JA, Hargrove P, Vanin EF, Nienhuis AW: Comparison of various envelope proteins for their ability to pseudotype lentiviral vectors and transduce primitive hematopoietic cells from human blood. Mol Ther. 2002, 5: 242-251. 10.1006/mthe.2002.0549.CrossRefPubMed
31.
Loo van der JC, Liu BL, Goldman AI, Buckley SM, Chrudimsky KS: Optimization of gene transfer into primitive human hematopoietic cells of granulocyte-colony stimulating factor-mobilized peripheral blood using low-dose cytokines and comparison of a gibbon ape leukemia virus versus an RD114-pseudotyped retroviral vector. Hum Gene Ther. 2002, 13: 1317-1330. 10.1089/104303402760128540.CrossRefPubMed
32.
Relander T, Johansson M, Olsson K, Ikeda Y, Takeuchi Y, Collins M, Richter J: Gene transfer to repopulating human CD34+ cells using amphotropic-, GALV-, or RD114-pseudotyped HIV-1-based vectors from stable producer cells. Mol Ther. 2005, 11: 452-459. 10.1016/j.ymthe.2004.10.014.CrossRefPubMed
33.
Ramezani A, Hawley TS, Hawley RG: Lentiviral vectors for enhanced gene expression in human hematopoietic cells. Mol Ther. 2000, 2: 458-469. 10.1006/mthe.2000.0190.CrossRefPubMed
34.
Salmon P, Kindler V, Ducrey O, Chapuis B, Zubler RH, Trono D: High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood. 2000, 96: 3392-3398.PubMed
35.
Liu Y, Chiriva-Internati M, Grizzi F, Salati E, Roman JJ, Lim S, Hermonat PL: Rapid induction of cytotoxic T-cell response against cervical cancer cells by human papillomavirus type 16 E6 antigen gene delivery into human dendritic cells by an adeno-associated virus vector. Cancer Gene Ther. 2001, 8: 948-957. 10.1038/sj.cgt.7700391.CrossRefPubMed
36.
Ponnazhagan S, Mahendra G, Curiel DT, Shaw DR: Adeno-associated virus type 2-mediated transduction of human monocyte-derived dendritic cells: implications for ex vivo immunotherapy. J Virol. 2001, 75: 9493-9501. 10.1128/JVI.75.19.9493-9501.2001.PubMedCentralCrossRefPubMed
37.
Chiriva-Internati M, Liu Y, Salati E, Zhou W, Wang Z, Grizzi F, Roman JJ, Lim SH, Hermonat PL: Efficient generation of cytotoxic T lymphocytes against cervical cancer cells by adeno-associated virus/human papillomavirus type 16 E7 antigen gene transduction into dendritic cells. Eur J Immunol. 2002, 32: 30-38. 10.1002/1521-4141(200201)32:1<30::AID-IMMU30>3.0.CO;2-E.CrossRefPubMed
38.
Veron P, Allo V, Riviere C, Bernard J, Douar AM, Masurier C: Major subsets of human dendritic cells are efficiently transduced using self-complementary adeno-associated viral vectors 1 and 2. J Virol. 2007, 81: 5385-5394. 10.1128/JVI.02516-06.PubMedCentralCrossRefPubMed
39.
Li X, Eastman EM, Schwartz RJ, Draghia-Akli R: Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences. Nat Biotechnol. 1999, 17: 241-245. 10.1038/6981.CrossRefPubMed
40.
Gonin P, Arandel L, Van Wittenberghe L, Marais T, Perez N, Danos O: Femoral intra-arterial injection: a tool to deliver and assess recombinant AAV constructs in rodents whole hind limb. J Gene Med. 2005, 7: 782-791. 10.1002/jgm.716.CrossRefPubMed
41.
Bartoli M, Roudaut C, Martin S, Fougerousse F, Suel L, Poupiot J, Gicquel E, Noulet F, Danos O, Richard I: Safety and efficacy of AAV-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2A. Mol Ther. 2006, 13: 250-259. 10.1016/j.ymthe.2005.09.017.CrossRefPubMed
42.
Follenzi A, Ailles LE, Bakovic S, Geuna M, Naldini L: Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet. 2000, 25: 217-222. 10.1038/76095.CrossRefPubMed
43.
Riviere C, Danos O, Douar AM: Long-term expression and repeated administration of AAV type 1, 2 and 5 vectors in skeletal muscle of immunocompetent adult mice. Gene Ther. 2006, 13: 1300-1308. 10.1038/sj.gt.3302766.CrossRefPubMed
44.
Xiao X, Li J, Samulski RJ: Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol. 1998, 72: 2224-2232.PubMedCentralPubMed
45.
Steinman RM: The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991, 9: 271-296. 10.1146/annurev.iy.09.040191.001415.CrossRefPubMed
46.
Steinman RM, Hawiger D, Nussenzweig MC: Tolerogenic dendritic cells. Annu Rev Immunol. 2003, 21: 685-711. 10.1146/annurev.immunol.21.120601.141040.CrossRefPubMed
47.
Pulendran B: Variegation of the immune response with dendritic cells and pathogen recognition receptors. J Immunol. 2005, 174: 2457-2465.CrossRefPubMed
48.
Case SS, Price MA, Jordan CT, Yu XJ, Wang L, Bauer G, Haas DL, Xu D, Stripecke R, Naldini L: Stable transduction of quiescent CD34(+)CD38(-) human hematopoietic cells by HIV-1-based lentiviral vectors. Proc Natl Acad Sci USA. 1999, 96: 2988-2993. 10.1073/pnas.96.6.2988.PubMedCentralCrossRefPubMed
49.
Stripecke R, Cardoso AA, Pepper KA, Skelton DC, Yu XJ, Mascarenhas L, Weinberg KI, Nadler LM, Kohn DB: Lentiviral vectors for efficient delivery of CD80 and granulocyte-macrophage- colony-stimulating factor in human acute lymphoblastic leukemia and acute myeloid leukemia cells to induce antileukemic immune responses. Blood. 2000, 96: 1317-1326.PubMed
50.
Lizee G, Gonzales MI, Topalian SL: Lentivirus vector-mediated expression of tumor-associated epitopes by human antigen presenting cells. Hum Gene Ther. 2004, 15: 393-404. 10.1089/104303404322959542.CrossRefPubMed
51.
Dullaers M, Thielemans K: From pathogen to medicine: HIV-1-derived lentiviral vectors as vehicles for dendritic cell based cancer immunotherapy. J Gene Med. 2006, 8: 3-17. 10.1002/jgm.846.CrossRefPubMed
Metadata
Title
Highly efficient transduction of human plasmacytoid dendritic cells without phenotypic and functional maturation
Authors
Philippe Veron
Sylvie Boutin
Samia Martin
Laurence Chaperot
Joel Plumas
Jean Davoust
Carole Masurier
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2009
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-7-10

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