Preferential retroviral-mediated transduction of EBV- and CMV-specific T cells after polyclonal T-cell activation.
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.
Sauce
D
D
INSERM U645/UPRES EA-2284, IFR 133 IBCT, Etablissement Français du Sang-Bourgogne/Franche-Comté, Besançon, France.
Mercier
P
P
Battini
J-L
JL
Ferrand
C
C
Certoux
J-M
JM
Manel
N
N
Taylor
N
N
Duperrier
A
A
Hervé
P
P
Tiberghien
P
P
Robinet
E
E
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D003587:Cytomegalovirus / Q000276:immunology*; D000939:Epitopes; D015316:Genetic Therapy / Q000379:methods*; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D012190:Retroviridae / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods*
D000939:Epitopes