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New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. 2005

Willem A Dik, and Karin Pike-Overzet, and Floor Weerkamp, and Dick de Ridder, and Edwin F E de Haas, and Miranda R M Baert, and Peter van der Spek, and Esther E L Koster, and Marcel J T Reinders, and Jacques J M van Dongen, and Anton W Langerak, and Frank J T Staal
Department of Immunology, Erasmus MC, 3015 GE Rotterdam, Netherlands.

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.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D015333 Gene Rearrangement, beta-Chain T-Cell Antigen Receptor Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors. T-Cell Antigen Receptor beta-Chain Gene Rearrangement,T-Lymphocyte Antigen Receptor beta-Chain Gene Rearrangement,Gene Rearrangement, beta-Chain T Cell Antigen Receptor,T Cell beta-Chain Gene Rearrangement,T Lymphocyte beta-Chain Gene Rearrangement,Gene Rearrangement, beta Chain T Cell Antigen Receptor,T Cell Antigen Receptor beta Chain Gene Rearrangement,T Cell beta Chain Gene Rearrangement,T Lymphocyte Antigen Receptor beta Chain Gene Rearrangement,T Lymphocyte beta Chain Gene Rearrangement
D015703 Antigens, CD Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation. CD Antigen,Cluster of Differentiation Antigen,Cluster of Differentiation Marker,Differentiation Antigens, Leukocyte, Human,Leukocyte Differentiation Antigens, Human,Cluster of Differentiation Antigens,Cluster of Differentiation Markers,Antigen Cluster, Differentiation,Antigen, CD,CD Antigens,Differentiation Antigen Cluster,Differentiation Marker Cluster,Marker Cluster, Differentiation
D016692 Receptors, Antigen, T-Cell, gamma-delta T-cell receptors composed of CD3-associated gamma and delta polypeptide chains and expressed primarily in CD4-/CD8- T-cells. The receptors appear to be preferentially located in epithelial sites and probably play a role in the recognition of bacterial antigens. The T-cell receptor gamma/delta chains are separate and not related to the gamma and delta chains which are subunits of CD3 (see ANTIGENS, CD3). Antigen Receptors, T-Cell, gamma-delta,T-Cell Receptors delta-Chain,T-Cell Receptors gamma-Chain,T-Cell Receptors, gamma-delta,TcR gamma-delta,Antigen T Cell Receptor, delta Chain,Antigen T Cell Receptor, gamma Chain,Receptors, Antigen, T Cell, gamma delta,T Cell Receptors, gamma delta,T-Cell Receptor delta-Chain,T-Cell Receptor gamma-Chain,T-Cell Receptor, gamma-delta,T Cell Receptor delta Chain,T Cell Receptor gamma Chain,T Cell Receptor, gamma delta,T Cell Receptors delta Chain,T Cell Receptors gamma Chain,TcR gamma delta,delta-Chain, T-Cell Receptor,delta-Chain, T-Cell Receptors,gamma-Chain, T-Cell Receptor,gamma-Chain, T-Cell Receptors,gamma-delta T-Cell Receptor,gamma-delta T-Cell Receptors,gamma-delta, TcR
D016694 Gene Rearrangement, delta-Chain T-Cell Antigen Receptor Ordered rearrangement of T-cell variable gene regions coding for the delta-chain of antigen receptors. T-Cell Antigen Receptor delta-Chain Gene Rearrangement,T-Lymphocyte Antigen Receptor delta-Chain Gene Rearrangement,Gene Rearrangement, delta-Chain T Cell Antigen Receptor,T Cell delta-Chain Gene Rearrangement,T Lymphocyte delta-Chain Gene Rearrangement,Gene Rearrangement, delta Chain T Cell Antigen Receptor,T Cell Antigen Receptor delta Chain Gene Rearrangement,T Cell delta Chain Gene Rearrangement,T Lymphocyte Antigen Receptor delta Chain Gene Rearrangement,T Lymphocyte delta Chain Gene Rearrangement

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