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Title: Analysing the role of lymphotoxin signalling in the development of lymphoid tissue microenvironments
Author: Glanville, Stephanie Helen
ISNI:       0000 0004 2702 5283
Awarding Body: The University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2008
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The formation of lympho-stromal microenvironments in primary and secondary lymphoid tissues is crucial for the correct and efficient functioning of the immune system. Induction and maintenance of these environments in the spleen requires lymphotoxin (LT)-dependent lymphostromal and Lymphoid Tissue inducer cell (LTi) -stromal interactions resulting in the secretion of chemokines. In contrast the LT-dependence of the thymus is unclear. We have developed an in vivo model to study the formation of splenic microenvironments by grafting embryonic spleens under the kidney capsule of adult mice. These grafts develop into phenotypically and functionally normal splenic tissue, exhibiting B-T segregation, mature stromal cell populations and a normal response to immunisation. Using this model we have shown that adult non-B, non-T cells are sufficient to provide LTa signals to developing splenic stromal cells and propose that adult LTi-like cells are responsible for this. Consistent with this idea we have also shown that LTi-like cells can develop from adult bone marrow precursors. In extending the study of microenvironments to the thymus, we identified key similarities to the spleen including the presence of LTi cells. We further found that in contrast to the spleen, LT signals in the thymus are not essential to maintain tissue organisation but that LTß receptor signals are required to optimise the medullary microenvironment and allow maximal emigration of mature thymocytes from the organ.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available