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Key factors in the organized chaos of early T cell development

Nature Immunology volume 8, pages 137–144 (2007)Cite this article

Abstract

A fundamental issue in T cell development is what controls whether a thymocyte differentiates into a γδ T cell or an αβ T cell, each defined by their distinct T cell receptor. Most likely, lessons learned in studying that issue will also provide insight into how the thymus produces T cell subsets with distinct functional and regulatory potentials. Here we review recent experiments, focusing on three factors that regulate thymocyte differentiation up to and including the expression of the first products of antigen receptor gene rearrangements. Those factors are the archetypal developmental regulator Notch, intrinsic signals emanating from antigen-receptor complexes, and trans conditioning, which reflects communication between different subsets of thymocytes. We also review new findings on the positive selection of γδ T cells and on extrathymic T cell development.

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Figure 1: Stages of T cell differentiation.
Figure 2: Waves of DN1–3 progenitors give rise to waves of γδ T cells that populate distinct anatomical sites.
Figure 3: The signal-strength and TCR-Notch synergy models.

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Acknowledgements

We thank many colleagues for their ideas and thoughts, in particular T. Silberzahn, B. Silva-Santos and R. Tigelaar. Supported by the Wellcome Trust.

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  1. King's College School of Medicine at Guy's Hospital, London, SE1 9RT, UK

    Adrian C Hayday

  2. Institute of Cell and Molecular Science, The London and Barts School of Medicine and Dentistry, Queen Mary College, London, E1 2AT, UK

    Daniel J Pennington

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Correspondence to Adrian C Hayday or Daniel J Pennington.

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Hayday, A., Pennington, D. Key factors in the organized chaos of early T cell development. Nat Immunol 8, 137–144 (2007). https://doi.org/10.1038/ni1436

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