New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling.

New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling.
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DOI:
10.1084/jem.20042524
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发表时间:
2005-06-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Staal FJ
Staal FJ
中科院分区:
其他
文献类型:
--
作者:
Dik WA;Pike-Overzet K;Weerkamp F;de Ridder D;de Haas EF;Baert MR;van der Spek P;Koster EE;Reinders MJ;van Dongen JJ;Langerak AW;Staal FJ

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To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human T cell development, we analyzed TCR gene rearrangements by quantitative PCR analysis in nine consecutive T cell developmental stages, including CD34+ lin− cord blood cells as a reference. The same stages were used for gene expression profiling using DNA microarrays. We show that TCR loci rearrange in a highly ordered way (TCRD-TCRG-TCRB-TCRA) and that the initiating Dδ2-Dδ3 rearrangement occurs at the most immature CD34+CD38−CD1a− stage. TCRB rearrangement starts at the CD34+CD38+CD1a− stage and complete in-frame TCRB rearrangements were first detected in the immature single positive stage. TCRB rearrangement data together with the PTCRA (pTα) expression pattern show that human TCRβ-selection occurs at the CD34+CD38+CD1a+ stage. By combining the TCR rearrangement data with gene expression data, we identified candidate factors for the initiation/regulation of TCR recombination. Our data demonstrate that a number of key events occur earlier than assumed previously; therefore, human T cell development is much more similar to murine T cell development than reported before.
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