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.
Preferential retroviral-mediated transduction of EBV- and CMV-specific T cells after polyclonal T-cell activation
Sauce, D.; Mercier, P.; Battini, J. L.; Ferrand, C.; Certoux, J. M.; Manel, N.; Taylor, N.; Duperrier, A.; Herve, P.; Tiberghien, P.; Robinet, E.
2004-06 / vol 11 / pages 1019-1022
protein; receptor; transduction; lymphocytes; t cell; expansion; leukemia-virus; selection; class-i; cmv; depletion; ebv; graft; thymidine kinase gene