Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Self-selection by genetically modified committed lymphocyte precursors reverses the phenotype of JAK3-deficient mice without myeloablation
Autore:
Bunting, KD; Lu, TH; Kelly, PF; Sorrentino, BP;
Indirizzi:
St Jude Childrens Res Hosp, Div Expt Hematol, Memphis, TN 38105 USA St Jude Childrens Res Hosp Memphis TN USA 38105 ol, Memphis, TN 38105 USA St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA St Jude Childrens Res Hosp Memphis TN USA 38105 em, Memphis, TN 38105 USA
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 17, volume: 11, anno: 2000,
pagine: 2353 - 2364
SICI:
1043-0342(200011)11:17<2353:SBGMCL>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; UMBILICAL-CORD BLOOD; X-CHROMOSOME INACTIVATION; LONG-TERM ENGRAFTMENT; RECEPTOR-GAMMA CHAIN; GENE-THERAPY; PERIPHERAL-BLOOD; MURINE MODEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Bunting, KD Amer Red Cross, Jerome H Holland Lab, Hematopoiesis Dept, 15601 Crabbs Branch Way, Rockville, MD 20855 USA Amer Red Cross 15601 Crabbs Branch Way Rockville MD USA 20855
Citazione:
K.D. Bunting et al., "Self-selection by genetically modified committed lymphocyte precursors reverses the phenotype of JAK3-deficient mice without myeloablation", HUM GENE TH, 11(17), 2000, pp. 2353-2364

Abstract

Janus kinase 3 (JAK3) is an essential component of cytokine receptor signal transduction pathways required for normal lymphocyte development and function. JAK3 deficiency in both mice and humans results in severe combined immunodeficiency (SCID) and increased susceptibility to opportunistic infections. We have previously shown that JAK3 gene transfer into irradiated recipients could restore immune function. However, since this toxic conditioningwould be undesirable for infants in a clinical application, we have testedwhether immune function could be restored in nonmyeloablated JAK3-deficient (-/-) mice. Murine JAK3 retroviral vectors were transduced into hematopoietic stem cells from the livers of newborn JAK3(-/-) mice. These cells werethen injected intraperitoneally into nonirradiated JAK3(-/-) neonates. Transduced cells were detectable in these mice at time points 4 to 6 months after injection and resulted in significant correction of T and B lymphocyte numbers and circulating immunoglobulin (Ig) levels. After immune challenge with a dose of influenza A virus that was lethal to nonmanipulated JAK3(-/-) mice, mice injected with transduced cells showed development of circulating virus-specific IgG and enhanced survival. This work shows that the largeselective advantage for JAK3-corrected lymphoid cells may be sufficient toovercome the need for myeloablative conditioning in JAK3 gene therapy protocols.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 09:07:58