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Titolo:
Costimulation of transduced T lymphocytes via T cell receptor-CD3 complex and CD28 leads to increased transcription of integrated retrovirus
Autore:
Pollok, KE; Van der Loo, JCM; Cooper, RJ; Kennedy, L; Williams, DA;
Indirizzi:
Indiana Univ, James Whitcomb Riley Hosp Children, Sch Med,Sect Pediat Hematol Oncol, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 at Res, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Howard Hughes Med Inst, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 d Inst, Indianapolis, IN 46202 USA
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 13, volume: 10, anno: 1999,
pagine: 2221 - 2236
SICI:
1043-0342(19990901)10:13<2221:COTTLV>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN ADENOSINE-DEAMINASE; MURINE LEUKEMIA-VIRUS; BONE-MARROW CELLS; PERIPHERAL-BLOOD LYMPHOCYTES; HEMATOPOIETIC STEM-CELLS; MEDIATED GENE-EXPRESSION; IN-VIVO EXPRESSION; TRANSGENE EXPRESSION; FIBRONECTIN FRAGMENTS; INTERFERON-GAMMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
70
Recensione:
Indirizzi per estratti:
Indirizzo: Williams, DA Indiana Univ, James Whitcomb Riley Hosp Children, Sch Med,Sect Pediat Hematol Oncol, Herman B Wells Ctr Pediat Res, 1044 W Walnut St,Room 402, Indianapolis, IN 46202 USA Indiana Univ 1044 W Walnut St,Room 402 Indianapolis IN USA 46202
Citazione:
K.E. Pollok et al., "Costimulation of transduced T lymphocytes via T cell receptor-CD3 complex and CD28 leads to increased transcription of integrated retrovirus", HUM GENE TH, 10(13), 1999, pp. 2221-2236

Abstract

Primary human T lymphocytes were transduced at high efficiency with the Moloney murine leukemia virus (Mo-MuLV) vector, LNC-mB7-1, in which an internal cytomegalovirus (CMV) promoter drives expression of the murine B7-1 cDNA. Compared with transduced T cells expanded in IL-2 or reactivated with soluble antibodies to CD3 or CD28, transgene expression was significantly increased after activation on immobilized anti-CD3 antibodies (CD3i) or by simultaneous activation on immobilized anti-CDS and anti-CD28 antibodies (CD3i/CD28i). A similar pattern of transgene expression was observed in T cells transduced with Mo-MuLV LNC-EGFP. Proviral copy number was maintained in LNC-mB7-1-transduced T cells expanded in IL-2 or reactivated on CD3i/CD28i. Substantial increases in LNC-mB7-1 steady state mRNA in reactivated T lymphocytes, compared with those maintained in IL-2, correlated with increased transcription of the LNC-mB7-1 proviral DNA. Furthermore, T cells transduced with the Mo-MuLV ZIPPGK-mADA, in which the mADA cDNA is driven by an internal human phosphoglycerate kinase (PGK) promoter, showed increases in steady state ZIPPGK-mADA RNA on reactivation. High levels of transgene expression were evident irrespective of cell cycle position in both CD4(+) and CD8(+) lymphocytes. After reactivation, increases in LNC-mB7-1 mRNA were observed in the presence of the protein synthesis inhibitor cycloheximide, indicating that proteins involved in upregulating transgene expression preexisted intransduced lymphocytes. Induction of transgene expression on CD3i/CD28i showed a dose-dependent decrease in transgene expression when incubated with selective protein kinase inhibitors. These data provide new insights into the mechanisms governing transgene expression driven by Mo-MuLV constructs containing internal promoters in transduced primary T lymphocytes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 16:10:56