Roberts, Natalie Amy (2011)
Ph.D. thesis, University of Birmingham.
Restricted to Repository staff only until 31 July 2015.
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.
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