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

作者：Blom B; Heemskerk MHM; Verschuren MCM; van Dongen JJM; Stegmann APA; Bakker AQ; Couwenberg F; Res PCM; Spits H^*

来源：The EMBO Journal, 1999, 18(10): 2793-2802.

DOI：10.1093/emboj/18.10.2793

• basic helix-loop-helix protein
• NK cell
• T cells
• thymus
• transcription

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 TCR alpha 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 TCR alpha beta but not into TCR gamma delta T cells. Furthermore, Id3 impedes expression of recombination activating genes and downregulates pre-T alpha mRNA, These observations suggest possible mechanisms by which Id3 overexpression can differentially affect development of pre-T cells into TCR alpha 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.

• 出版日期1999-5-17