Abstract
Graft-versus-host disease, resulting from the T cells present in allogeneic hematopoietic stem cell (HSC) inoculums, can potentially be treated if a suicide gene has been introduced into the donor T cells. However, the diversity and functionality of the transfused T-cell population, including EBV- (EBV-T) and CMV-specific (CMV-T) CD8+ T cells, which are particularly important for immunosuppressed individuals undergoing HSC transplants, are often modified by the gene transfer protocol. Here, we show that following polyclonal T-cell activation, EBV-T and CMV-T cells are preferentially transduced by oncoretroviral vectors, as compared to the bulk CD8+ T-cell population. This preferential transduction is associated with higher surface levels of PiT-2, the receptor for the amphotropic envelope with which the virions are pseudotyped. Moreover, EBV-T and CMV-T cells proliferate more extensively as compared to bulk CD8+ T cells. Thus, retroviral-mediated transduction can be biased toward a given antigenic specificity, even under conditions of polyclonal stimulation.
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Acknowledgements
This work was supported by the Programme Hospitalier de Recherche Clinique (PHRC 2000 #RC39), the Association Française contre la Myopathie and the Ministère de l’Enseignement Supérieur et de la Recherche (Centre Réseau de Développement des Thérapies Géniques (CRTG)), the Association pour la Recherche sur le Cancer (Grants # 4350 & # 7665), the Ligue contre le Cancer, Comité du Doubs and the European Community (Biomed contract # CT97-2074 and QLK3-CT-2001-01265). Patricia Mercier has benefited from a grant from the Ligue Contre le Cancer, Comité du Doubs. We also thank Dr Mark Bonyhadi (Xcyte Therapies Inc., Seattle, WA, USA) for providing us with CD3/CD28 beads.
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Sauce, D., Mercier, P., Battini, JL. et al. Preferential retroviral-mediated transduction of EBV- and CMV-specific T cells after polyclonal T-cell activation. Gene Ther 11, 1019–1022 (2004). https://doi.org/10.1038/sj.gt.3302273
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DOI: https://doi.org/10.1038/sj.gt.3302273
