Disruption of aß but not of ?d T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors.

Autor: Blom, Bianca, Heemskerk, Mirjam H. M., Verschuren, Martie C. M., van Dongen, Jacques J. M., Stegmann, Alexander P. A., Bakker, Arjen Q., Couwenberg, Franka, Res, Pieter C. M., Spits, Hergen
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Zdroj: EMBO Journal; 5/17/99, Vol. 18 Issue 10, p2793-2802, 10p
Abstrakt: 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&lpha;β and γδ 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&lpha;β but not into TCRγδ T cells. Furthermore, Id3 impedes expression of recombination activating genes and downregulates pre-Tα mRNA. These observations suggest possible mechanisms by which Id3 overexpression can differentially affect development of pre-T cells into TCR&lpha;β and γδ 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index