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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2002-11-3407. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3407v1 102/4/1241    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 Sauce, D. Articles by Robinet, E. Search for Related Content PubMed PubMed Citation Articles by Sauce, D. Articles by Robinet, E. Related Collections Immunobiology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2003, Vol. 102, No. 4, pp. 1241-1248 GENE THERAPY Retrovirus-mediated gene transfer in polyclonal T cells results in lower apoptosis and enhanced ex vivo cell expansion of CMV-reactive CD8 T cells as compared with EBV-reactive CD8 T cells Delphine Sauce, Nathalie Rufer, Patricia Mercier, Marie Bodinier, Jean-Paul Rémy-Martin, Anne Duperrier, Christophe Ferrand, Patrick Hervé, Pedro Romero, François Lang, Pierre Tiberghien, and Eric Robinet From the Institut National de la Santé et de la Recherche Médicale (INSERM) EPI-0119/Unité Propre de Recherche de l'Enseignement Superieur (UPRES) EA-2284, Etablissement Français du Sang-Bourgogne/Franche-Comté, Besançon, France; National Center of Competence in Research (NCCR) Molecular Oncology, Swiss Institute for Cancer Research, Epalinges, Switzerland; INSERM U463, Institut de Biologie, Nantes, France; and Multidisciplinary Oncology Center, University Hospital, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. To modulate alloreactivity after hematopoietic stem cell transplantation, "suicide" gene-modified donor T cells (GMCs) have been administered with an allogeneic T-cell–depleted marrow graft. We previously demonstrated that such GMCs, generated after CD3 activation, retrovirusmediated transduction, and G418 selection, had an impaired Epstein-Barr virus (EBV) reactivity, likely to result in an altered control of EBV-induced lymphoproliferative disease. To further characterize the antiviral potential of GMCs, we compared the frequencies of cytomegalovirus (CMV)–specific CD8+ T (CMV-T) cells and EBV-specific CD8+ T (EBV-T) cells within GMCs from CMV- and EBV-double seropositive donors. Unlike anti-EBV responses, the anti-CMV responses were not altered by GMC preparation. During the first days of culture, CMV-T cells exhibited a lower level of CD3-induced apoptosis than did EBV-T cells. In addition, the CMV-T cells escaping initial apoptosis subsequently underwent a higher expansion rate than EBV-T cells. The differential early sensitivity to apoptosis could be in relation to the "recent activation" phenotype of EBV-T cells as evidenced by a higher level of CD69 expression. Furthermore, EBV-T cells were found to have a CD45RA–CD27+CCR7– effector memory phenotype, whereas CMV-T cells had a CD45RA+CD27–CCR7– terminal effector phenotype. Such differences could be contributive, because bulk CD8+CD27– cells had a higher expansion than did bulk CD8+CD27+ cells. Overall, ex vivo T-cell culture differentially affects apoptosis, long-term proliferation, and overall survival of CMV-T and EBV-T cells. Such functional differences need to be taken into account when designing cell and/or gene therapy protocols involving ex vivo T-cell manipulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Deschamps, P. Mercier-Lethondal, J. M. Certoux, C. Henry, B. Lioure, C. Pagneux, J. Y. Cahn, E. Deconinck, E. Robinet, P. Tiberghien, et al. Deletions within the HSV-tk transgene in long-lasting circulating gene-modified T cells infused with a hematopoietic graft Blood, December 1, 2007; 110(12): 3842 - 3852. [Abstract] [Full Text] [PDF] F. Ciceri, C. Bonini, S. Marktel, E. Zappone, P. Servida, M. Bernardi, A. Pescarollo, A. Bondanza, J. Peccatori, S. Rossini, et al. Antitumor effects of HSV-TK engineered donor lymphocytes after allogeneic stem-cell transplantation Blood, June 1, 2007; 109(11): 4698 - 4707. [Abstract] [Full Text] [PDF] N. Schaft, B. Lankiewicz, J. Drexhage, C. Berrevoets, D. J. Moss, V. Levitsky, M. Bonneville, S. P. Lee, A. J. McMichael, J.-W. Gratama, et al. T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFN{gamma} production Int. Immunol., April 1, 2006; 18(4): 591 - 601. [Abstract] [Full Text] [PDF]

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