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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1818-1827. Prepublished online as a Blood First Edition Paper on November 1, 2005; DOI 10.1182/blood-2005-01-0339. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0339v1 107/5/1818    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Van Gulck, E. R. A. Articles by Vanham, G. Search for Related Content PubMed PubMed Citation Articles by Van Gulck, E. R. A. Articles by Vanham, G. Related Collections Immunobiology Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Efficient stimulation of HIV-1–specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins Ellen R. A. Van Gulck, Peter Ponsaerts, Leo Heyndrickx, Katleen Vereecken, Filip Moerman, Ann De Roo, Robert Colebunders, Glenn Van den Bosch, Dirk R. Van Bockstaele, Viggo F. I. Van Tendeloo, Sabine Allard, Bernard Verrier, Concepción Marañón, Guillaume Hoeffel, Anne Hosmalin, Zwi N. Berneman, and Guido Vanham From the HIV and Retrovirology Research Unit, Department of Microbiology, Institute of Tropical Medicine of Antwerp (ITMA), Belgium; Laboratory of Experimental Hematology, Faculty of Medicine, University of Antwerp (UA), Antwerp University Hospital (UZA), Belgium; AIDS Clinic, Clinical Department, ITMA, Belgium; Laboratory of Physiology and Immunology, Brussels, Belgium; Centre National de la Recherche Scientifique (CNRS)–bioMérieux, Fédération Romande pour l'Energie (FRE) 2736, Instituts Fédératifs de Recherche (IFR) 128, Tour Centre d'Etudes et de Recherches en Virologie et Immunologie (CERVI), Lyon, France; Antigen Presentation by Dendritic Cell Group, Département d'Immunologie, Institut Cochin, Institut National de la Santé et de la Recherche Médicale (INSERM) U567, CNRS Unité mixte de Recherche (UMR) 8104, Université Paris V, France; and Department of Biomedical Sciences, Faculty of Pharmaceutical, Veterinary and Biomedical Sciences, University of Antwerp, Belgium. Infection with human immunodeficiency virus type 1 (HIV-1) is characterized by dysfunction of HIV-1–specific T cells. To control the virus, antigen-loaded dendritic cells (DCs) might be useful to boost and broaden HIV-specific T-cell responses. In the present study, monocyte-derived DCs from nontreated HIV-1–seropositive patients were electroporated with codon-optimized ("humanized") mRNA encoding consensus HxB-2 (hHXB-2) Gag protein. These DCs elicited a strong HIV-1 Gag-specific interferon- (IFN-) response by an HLA-A2–restricted CD8+ T-cell line. Moreover, hHXB-2 gag mRNA-electroporated DCs also triggered IFN- secretion by autologous peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and CD8+ T cells from all patients tested. Next, a novel strategy was developed using autologous virus sequences. Significant specific IFN- T-cell responses were induced in all patients tested by DCs electroporated with patients' autologous polymerase chain reaction (PCR)–amplified and in vitro–transcribed proviral and plasma viral mRNA encoding either Gag or Env. The stimulatory effect was seen on PBMCs, CD8+ T cells, and CD4+ T cells, demonstrating both major histocompatibility complex (MHC) class I and MHC class II antigen presentation. Moreover, a significant interleukin-2 (IL-2) T-cell response was induced by DCs electroporated with hHxB-2 or proviral gag mRNA. These findings open a major perspective for the development of patient-specific immunotherapy for HIV-1 disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. M. Melhem, S. M. Gleason, X. D. Liu, and S. M. Barratt-Boyes High-Level Antigen Expression and Sustained Antigen Presentation in Dendritic Cells Nucleofected with Wild-Type Viral mRNA but Not DNA Clin. Vaccine Immunol., September 1, 2008; 15(9): 1337 - 1344. [Abstract] [Full Text] [PDF] E. R. Van Gulck, G. Vanham, L. Heyndrickx, S. Coppens, K. Vereecken, D. Atkinson, E. Florence, I. Kint, Z. N. Berneman, and V. V. Tendeloo Efficient In Vitro Expansion of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses by gag mRNA-Electroporated Dendritic Cells from Treated and Untreated HIV Type 1-Infected Individuals J. Virol., April 1, 2008; 82(7): 3561 - 3573. [Abstract] [Full Text] [PDF] Z. N. Berneman, E. R. Van Gulck, L. Heyndrickx, P. Ponsaerts, V. F.I. Van Tendeloo, and G. Vanham Induction of Potentially Protective HIV-Specific T-Cell Responses In Vitro by Gag mRNA-Electroporated Dendritic Cells. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 1261 - 1261. [Abstract] [PDF] D. Finzi, S. F. Plaeger, and C. W. Dieffenbach Defective Virus Drives Human Immunodeficiency Virus Infection, Persistence, and Pathogenesis. Clin. Vaccine Immunol., July 1, 2006; 13(7): 715 - 721. [Full Text] [PDF]

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