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

Enforced expression of Id3, which has the capacity to inhibit many basic he lix-loop-helix (bHLH) transcription factors, in human CD34(+) hematopoietic progenitor cells that have not undergone T cell receptor (TCR) gene rearra ngements inhibits development of the transduced cells into TCR alpha beta a nd gamma delta cells in a fetal thymic organ culture (FTOC), Here we docume nt 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 re combination activating genes and downregulates pre-T alpha mRNA, These obse rvations suggest possible mechanisms by which Id3 overexpression can differ entially affect development of pre-T cells into TCR alpha beta and gamma de lta cells. We also observed that cell surface CD4(-)CD8(-)CD3(-)cells with rearranged TCR genes developed from Id3-transduced but not from control-tra nsduced 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 r equired to control T cell development after the T/NK developmental checkpoi nt.