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

• Published in: The EMBO journal 1999-05, Vol.18 (10), p.2793-2802
• Main Authors: Blom, B, Heemskerk, M H, Verschuren, M C, van Dongen, J J, Stegmann, A P, Bakker, A Q, Couwenberg, F, Res, P C, Spits, H
• Format: Article
• Language: English
• Subjects: Antigens, CD - immunology; Cell Differentiation; Cells, Cultured; Gene Expression Regulation; Gene Rearrangement, T-Lymphocyte - genetics; Helix-Loop-Helix Motifs; Hematopoietic Stem Cells - metabolism; Humans; Inhibitor of Differentiation Proteins; Neoplasm Proteins; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, gamma-delta - genetics; Retroviridae - genetics; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - metabolism; Thymus Gland; Transcription Factors - genetics; Transduction, Genetic
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1093/emboj/18.10.2793

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.