New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling
| Autor: | Floor Weerkamp, Marcel J. T. Reinders, Esther E. L. Koster, Jacques J.M. van Dongen, Anton W. Langerak, Willem A. Dik, Peter J. van der Spek, Miranda R. M. Baert, Dick de Ridder, Karin Pike-Overzet, Frank J. T. Staal, Edwin F. E. de Haas |
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| Přispěvatelé: | Immunology, Pathology |
| Rok vydání: | 2005 |
| Předmět: |
T cell
Cellular differentiation T-Lymphocytes Immunology Gene Rearrangement delta-Chain T-Cell Antigen Receptor Biology Mice Antigens CD Gene expression medicine Immunology and Allergy Animals Humans Gene Rearrangement beta-Chain T-Cell Antigen Receptor Gene Cells Cultured Oligonucleotide Array Sequence Analysis Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling T-cell receptor Brief Definitive Report hemic and immune systems Cell Differentiation Receptors Antigen T-Cell gamma-delta Gene rearrangement Molecular biology Gene expression profiling medicine.anatomical_structure Gene Expression Regulation Genes T-Cell Receptor beta |
| Zdroj: | Journal of Experimental Medicine, 201(11), 1715-1723. Rockefeller University Press The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | 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 Ddelta2-Ddelta3 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 (pTalpha) expression pattern show that human TCRbeta-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. |
| Databáze: | OpenAIRE |
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