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Determining versus T cell development
Maria Ciofani* and Juan Carlos Ziga-Pflcker
Abstract | The thymus produces several types of functionally distinct T cell subsets. However, at a more fundamental level only two genetically distinct T cell lineages exist: the and
T cell lineages. Precisely how these two T cell lineages are generated from common thymocyte progenitor cells remains to be fully elucidated and is under intense investigation. Here, we highlight recent findings that have helped to provide important clues to the mechanisms that underpin the generation of T cells in the mouse thymus.
T cell development occurs in the thymus and relies on the specialized microenvironment that is provided by this organ1. The differentiation of immature thymocytes in the thymus is mediated by the integration of intrinsic signals, which are generated downstream of the T cell receptor (TCR), and extrinsic signals, which are obtained from numerous interactions of T cell progenitors with stromal cells and other thymocytes. This unique combination of signals has provided the intellectual basis of distinct models for the lineage specification of T cell subsets at crucial branch points in T cell development.
Two fundamentally distinct T cell lineages are generated in the thymus and are uniquely defined by their expression of an TCR or a TCR. These separate T cell lineages initially arise from common precursor cells that lack expression of CD4 and CD8 co-receptors and are known as double-negative (DN) thymocytes. In mice, developmental transitions in this early subset of thymocytes coincide with changes in the expression of several cell surface markers, mainly http://www.uniprot.org/uniprot/P24807
Web End =CD24 , http://www.uniprot.org/uniprot/P01590
Web End =CD25 , http://www.uniprot.org/uniprot/P15379
Web End =CD44 and http://www.uniprot.org/uniprot/P05532
Web End =CD117 (also known as KIT) (FIG. 1).
The heterogeneity of the DN thymocyte compartment has led to further subdivision of these cells with the aim of identifying precursor subsets that have defined developmental potential(s), for example, DN1aDN1e, DN2, DN3a and DN3b (also known as DN3E and DN3L, respectively)24. Transition from the DN1 to DN2 stage marks the initiation of gene rearrangement at the TCR, TCR and TCR gene loci; a process that is completed in DN3 cells5. The DN3 stage is an obligatory checkpoint at which expression of the pre-T cell receptor (pre-TCR) or the TCR results in...