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Lymphostromal interactions in the development and function of thymic epithelial cells

Roberts, Natalie Amy (2011)
Ph.D. thesis, University of Birmingham.

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The thymus is a primary lymphoid organ that supports the production, differentiation and selection of self-tolerant T cells from immature precursors of extrathymic origin. T cell development is a dynamic process involving the movement of thymocytes through specialised regions of the thymus, each directing distinct developmental stages. The formation of these microenvironments is crucial for providing the ordered and continuous signalling required to drive the non-cell autonomous process of T cell development. The development of thymocytes and thymic epithelial cells (TEC) are interdependent processes involving reciprocal signalling termed “thymic crosstalk”.
Using novel in vitro and in vivo experimental techniques we elucidated novel processes in the regulation of thymic epithelial cell development. We corroborated the importance of thymic crosstalk by revealing a new role for innate like  T cells in influencing medullary thymic epithelial cell development. Furthermore, this study argues against a specific time frame for the occurrence of thymic crosstalk by demonstrating that adult thymic epithelium retains its receptivity to lymphostromal signalling. In addition, we have recognised the importance of intrathymic niches in regulating early T cell progenitor development.
Collectively these data have provided an insight into the development of the thymic epithelium and thus have important implications in relation to developing rejuvenation strategies for the atrophied thymus and following ablative therapy.

Type of Work:Ph.D. thesis.
Supervisor(s):Anderson, Graham and Jenkinson, Eric
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:Institute of Biomedical Research, Department of Anatomy
Subjects:QM Human anatomy
RC Internal medicine
Institution:University of Birmingham
ID Code:2902
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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