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Thymocyte Development

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Mathematical Models and Immune Cell Biology

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Abstract

T cell development within the thymus involves the dynamic interaction of thymocytes with a unique heterogeneous microenvironment formed predominantly by a three-dimensional network of specialized thymic epithelium. Multiple developmental checkpoints have been identified during thymocyte maturation, including selective recruitment to the thymus, αβ versus γδ T cell fate decisions, positive and negative selection and finally regulated egress of mature T cells from the thymus to the periphery. The controlled migration of thymocytes within the thymus ensures that developing T cells undergo a series of tightly-regulated interactions with stromal cells of the thymus, ensuring that, firstly, only cells bearing a functional TCR are selected for survival and onward differentiation via positive selection and, secondly, that autoreactive T cells capable of responding to self-antigens and causing autoimmune disease are deleted via negative selection. The stringent selection mechanisms enforced within the thymus are demonstrated by the fact that only 2–5% of thymocytes generated within the thymus mature to form naïve T cells capable of forming a functional, self-tolerant component of the peripheral adaptive immune system. Whilst many of the developmental processes occurring during thymocyte development have become elucidated over the past several years, systems directed towards modelling the dynamic migratory patterns and real-time cellular interactions will radically advance our understanding of how such pivotal cells of the immune system are generated.

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Authors and Affiliations

  1. Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, Birmingham, B15 2TT, UK

    William Jenkinson

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  1. William Jenkinson
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  2. Eric Jenkinson
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  3. Graham Anderson
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Correspondence to William Jenkinson .

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Editors and Affiliations

  1. School of Mathematics, Dept. Applied Mathematics, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, United Kingdom

    Carmen Molina-París

  2. School of Mathematics, Dept. Applied Mathematics, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, United Kingdom

    Grant Lythe

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Jenkinson, W., Jenkinson, E., Anderson, G. (2011). Thymocyte Development. In: Molina-París, C., Lythe, G. (eds) Mathematical Models and Immune Cell Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7725-0_1

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