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Titolo:
Enforced expression of GATA-3 severely reduces human thymic cellularity
Autore:
Taghon, T; De Smedt, M; Stolz, F; Cnockaert, M; Plum, J; Leclercq, G;
Indirizzi:
State Univ Ghent Hosp, Dept Clin Chem Microbiol & Immunol, B-9000 Ghent, Belgium State Univ Ghent Hosp Ghent Belgium B-9000 mmunol, B-9000 Ghent, Belgium
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 8, volume: 167, anno: 2001,
pagine: 4468 - 4475
SICI:
0022-1767(20011015)167:8<4468:EEOGSR>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
BONE-MARROW TRANSPLANTATION; T-CELL REGENERATION; TRANSCRIPTION FACTOR GATA-3; HUMAN CORD-BLOOD; THYMOCYTE DIFFERENTIATION; GENE; MICE; LINEAGE; IDENTIFICATION; REPERTOIRE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Leclercq, G State Univ Ghent Hosp, Dept Clin Chem Microbiol & Immunol, Block A,4th Floor,Pintelaan 185, B-9000 Ghent, Belgium State Univ Ghent Hosp Block A,4th Floor,Pintelaan 185 Ghent Belgium B-9000
Citazione:
T. Taghon et al., "Enforced expression of GATA-3 severely reduces human thymic cellularity", J IMMUNOL, 167(8), 2001, pp. 4468-4475

Abstract

Following bone marrow transplantation, patients often suffer from immune incompetence by reduced or late T cell development. Moreover, adult bone marrow stern cells have a lower capacity to generate T cells compared with fetal liver- and umbilical cord blood-derived progenitors. Therefore, enhancing thymic-dependent T cell generation might hold great therapeutic potential. GATA-3 is a transcription factor that is essential in T cell development. In this study we examined the therapeutic potential of GATA-3 to enhance Tcell generation by overexpressing GATA-3 in T cell progenitors followed byfetal thymic organ culture (FTOC). We observed that early during FTOC, there was an enhanced differentiation toward the double positive stage of T cell development. From day 10 of FTOC, however, overexpression of GATA-3 induced a severe reduction in thymic cellularity, which probably correlates with the absence of a functional TCR-beta chain. We further show that the frequency of apoptosis was increased in GATA-3-transduced thymocytes. Despite the absence of a functional TCR-beta chain, GATA-3 transduced progenitors were able to differentiate into CD8 beta (+) double positive thymocytes. Thisstudy shows that a strictly regulated expression of GATA-3 is essential for normal T cell development and this puts severe restrictions on the potential therapeutic use of continuously overexpressed GATA-3.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 18:34:46