The stromal cells of the thymus provide the microenvironments necessary for T-cell maturation and repertoire selection. The thymic stroma consists of distinct subpopulations of epithelial and non-epithelial cells which regulate the development of thymocytes. This work evaluates the hypothesis that the mature epithelial subpopulations present in the adult thymus derive from a progenitor cell population in the thymic primordium marked by two monoclonal antibodies. MTS2O and MTS24. Analysis of cells in the embryonic day 12.5 (E12.5) thymic primordium showed that MTS2O and MTS24 were expressed by approximately 50% of epithelial cells and these cells did not express markers associated with terminally differentiated thymic epithelium Furthermore MTS2O and MTS24 were strongly down regulated during thymus ontogeny, and in the adult, reacted only with rare medullary epithelial cells. The MTS20/24<sup>+</sup> population purified from E12.5 thymi expressed <i>whn, Pax1, </i> <i>Pax9 </i>and <i>Hoxa3, </i>transcription factors required during early thymus development. To assess the functional potential of MTS20/24<sup>+</sup> cells, purified E12.5 thymus cell populations were grafted under the kidney capsule of <i>nude </i>mice. Immunohistochemical analysis of MTS2O/24<sup>+ </sup>cell grafts demonstrated the presence of mature cortical and medullary thymic epithelium. These grafts were also capable of attracting lymphoid progenitors and of supporting thymocyte differentiation. Furthermore, mature single positive T-cells were present in the periphery of <i>nude </i>mice grafted with MTS20/24<sup>+</sup> cells indicating that these cells can confer thymus function to athymic recipients. The MTS2O/24<sup>-</sup> cells from E12.5 thymi could fulfil none of these functions. These data demonstrate that the MTS2O/24<sup>+</sup> population from the thymic primordium contains progenitor cells that can give rise to the major epithelial populations and generate a functional thymic microenvironment.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:641529 |
| Date | January 2001 |
| Creators | Bennett, Andrea Ruth |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/13995 |
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