Disruption of αβ but not of γδ T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors
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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DOI：
10.1093/emboj/18.10.2793
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发表时间：
1999-05-17
期刊：
影响因子：
11.4
通讯作者：
Spits, H
中科院分区：
文献类型：
--
作者：
Blom, B;Heemskerk, MHM;Spits, H
Id 3具有抑制许多碱性螺旋-环-螺旋（bHLH）转录因子的能力，在未经历T细胞受体（TCR）基因重排的人CD 34（+）造血祖细胞中的强化表达抑制了在胎儿胸腺器官培养物（FTOC）中转导的细胞发育成TCR α β和γ δ细胞。在已经启动TCR基因重排的祖细胞（前T细胞）中，抑制向TCR α β但不向TCR γ δ T细胞的发育。此外，Id 3阻碍重组激活基因的表达并下调前-T α mRNA。这些观察结果表明Id 3过表达可以差异性地影响前-T细胞向TCR α β和γ δ细胞的发育的可能机制。我们还观察到，在FTOC中，细胞表面具有重排的TCR基因的CD 4（-）CD 8（-）CD 3（-）细胞由Id 3转导的前T细胞而不是由对照转导的前T细胞发育而来，这些细胞具有自然杀伤（NK）细胞和前T细胞的性质。这些发现表明，bHLH因子需要控制T/NK发育检查点后的T细胞发育。
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 TCR alpha 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 TCR alpha beta but not into TCR gamma delta T cells. Furthermore, Id3 impedes expression of recombination activating genes and downregulates pre-T alpha mRNA, These observations suggest possible mechanisms by which Id3 overexpression can differentially affect development of pre-T cells into TCR alpha 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.