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

WA Dik, K Pike-Overzet, F Weerkamp… - The Journal of …, 2005 - rupress.org
WA Dik, K Pike-Overzet, F Weerkamp, D De Ridder, EFE De Haas, MRM Baert…
The Journal of experimental medicine, 2005rupress.org
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 …
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+CD38CD1a 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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