The development and function of thymic microenvironments

Shakib, Saba (2009). The development and function of thymic microenvironments. University of Birmingham. Ph.D.

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Abstract

The thymus is organised into distinct microenvironments, and trafficking through these regions enables thymocytes to receive essential signals for the generation of a diverse and self-tolerant T-cell repertoire. Thymic epithelial cells (TEC) represent a key stromal cell type during defined stages in T cell development, yet the mechanisms regulating their development are only partly understood. An ontogenetic approach was employed to study stages of cortical thymic epithelial cell (cTEC) development. This study identifies a previously unreported population of cTEC progenitors expressing CD205 and 5T and has defined distinct checkpoints in the development of the cTEC lineage. Furthermore, the importance of thymic crosstalk during specific stages of cTEC development and also the requirement for RANK-RANKL signalling for the development of various medullary thymic epithelial cell (mTEC) subsets has also been defined. Additionally, the importance of chemokine-mediated signalling for the establishment and compartmentalisation of the thymus has been highlighted by employing laser capture microdissection and studying thymus microenvironments in mice deficient for particular chemokine related signalling pathways. Overall this study has provided novel insight into the development of the thymic cortex and will help to understand how these cells become specialised in their ability to support positive selection of developing T cells.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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