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Titolo:
Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector
Autore:
Dardalhon, V; Jaleco, S; Rebouissou, G; Ferrand, C; Skander, N; Swainson, L; Tiberghien, P; Spits, H; Noraz, N; Taylor, N;
Indirizzi:
Inst Mol Genet, CNRS UMR 5535, IFR24, F-34293 Montpellier 5, France Inst Mol Genet Montpellier France 5 IFR24, F-34293 Montpellier 5, France EFS Bourgogne France Comte, Lab Therepeut Immunomol, Besancon, France EFS Bourgogne France Comte Besancon France Immunomol, Besancon, France Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands Netherlands Canc Inst Amsterdam Netherlands NL-1066 CX rdam, Netherlands
Titolo Testata:
BLOOD
fascicolo: 3, volume: 96, anno: 2000,
pagine: 885 - 893
SICI:
0006-4971(20000801)96:3<885:HEGTIN>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
GREEN FLUORESCENT PROTEIN; HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD LYMPHOCYTES; RECEPTOR-GAMMA-CHAIN; MAMMALIAN-CELLS; IN-VITRO; REVERSE-TRANSCRIPTASE; FIBRONECTIN FRAGMENTS; HEMATOPOIETIC-CELLS; RETROVIRAL VECTORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Taylor, N Inst Mol Genet, CNRS UMR 5535, IFR24, 1919 Route Mende, F-34293 Montpellier 5, France Inst Mol Genet 1919 Route Mende Montpellier France 5 5, France
Citazione:
V. Dardalhon et al., "Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector", BLOOD, 96(3), 2000, pp. 885-893

Abstract

Retroviral vectors based on the Moloney murine leukemia virus (MULV) have become the primary tool for gene delivery into hematopoietic cells, but clinical trials have been hampered by low transduction efficiencies. Recently,we and others have shown that gene transfer of MuLV-based vectors into T cells can be significantly augmented using a fibronectin-facilitated protocol. Nevertheless, the relative abilities of naive (CD45RA(+)) and memory (CD45RO(+)) lymphocyte subsets to be transduced has not been assessed, Although naive T cells demonstrate a restricted cytokine profile following antigenstimulation and a decreased susceptibility to infection with human immunodeficiency virus, it was not clear whether they could be efficiently infected with a MuLV vector. This study describes conditions that permitted gene transfer of an enhanced green fluorescent protein-expressing retroviral vector in more than 50% of naive umbilical cord (UC) blood and peripheral blood(PB)T cells following CD3/CD28 ligation, Moreover, treatment of naive T cells with interleukin-7 resulted in the maintenance of a CD45RA phenotype and gene transfer levels ap preached 20%, Finally, it was determined that parameters for optimal transduction of CD45RA+ T cells isolated from PB UC blood differed: transduction of the UC cells was significantly increased by the presence of autologous mononuclear cells (24.5% versus 56.5%), Because naive T cells harbor a receptor repertoire that allows them to respond to novel antigens, the development of protocols targeting their transduction is crucial for gene therapy applications, This approach will also allow the functions of exogenous genes to be evaluated in primary nontransformed naive Tcells, (C) 2000 by The American Society of nematology.

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Documento generato il 27/09/20 alle ore 21:50:28