Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors.
EMBO J
; 18(10): 2793-802, 1999 May 17.
Article
em En
| MEDLINE
| ID: mdl-10329625
ABSTRACT
Enforced expression of Id3, which has the capacity to inhibit many basic helix-loop-helix (bHLH) transcription factors, in human CD34(+) hematopoietic progenitor cells that have not undergone T cell receptor (TCR) gene rearrangements inhibits development of the transduced cells into TCRalpha beta and gamma delta cells in a fetal thymic organ culture (FTOC). Here we document that overexpression of Id3, in progenitors that have initiated TCR gene rearrangements (pre-T cells), inhibits development into TCRalpha beta but not into TCRgamma delta T cells. Furthermore, Id3 impedes expression of recombination activating genes and downregulates pre-Talpha mRNA. These observations suggest possible mechanisms by which Id3 overexpression can differentially affect development of pre-T cells into TCRalpha beta and gamma delta cells. We also observed that cell surface CD4(-)CD8(-)CD3(-) cells with rearranged TCR genes developed from Id3-transduced but not from control-transduced pre-T cells in an FTOC. These cells had properties of both natural killer (NK) and pre-T cells. These findings suggest that bHLH factors are required to control T cell development after the T/NK developmental checkpoint.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Células-Tronco Hematopoéticas
/
Linfócitos T
/
Receptores de Antígenos de Linfócitos T gama-delta
/
Receptores de Antígenos de Linfócitos T alfa-beta
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article