Disruption of αβ but not of γδ 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 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 TCRαβ 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 TCRαβ 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 TCRαβ 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.

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