Disruption of αβ but not of γδ T cell development by overexpression of the helix–loop–helix protein Id3 in committed T cell progenitors

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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 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.