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 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 TCRalpha 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 TCRalpha beta but not into TCRgamma delta T cells. Furthermore, Id3 impedes expression of recombination activating genes and downregulates pre-Talpha mRNA. These observations suggest possible mechanisms by which Id3 overexpression can differentially affect development of pre-T cells into TCRalpha 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.
D015703:Antigens, CD / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D018257:Helix-Loop-Helix Motifs; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland; D014157:Transcription Factors / Q000235:genetics*; D014161:Transduction, Genetic