Exploring adaptive – like biology in human and murine уδ T cells


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Zeglam, Ameenah A (2022). Exploring adaptive – like biology in human and murine уδ T cells. University of Birmingham. Ph.D.

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Human Vδ1 уδ T cells in the blood have been observed to have an adaptive biology but many questions about them are difficult to explore in humans. Therefore mouse models may be useful to introduce. In this thesis I aim to investigate the presence and characteristics of murine adaptive-like уδ T cells, in both steady state mice and following infections.

In healthy mice we identified naïve (CD62L- CD44+), central memory-like (cm-like) (CD62L+ CD44+) and effector (CD62L- CD44+) уδ T cells, all of which were present in lymphoid tissue, whilst only effector cells were present in the gut. We characterised the populations through their marker expression, migratory capacity and development and found their characteristics often aligning with a naïve and effector phenotype. Interestingly, the TCR repertoire of all three populations was very polyclonal with few expansions.

In acute and chronic infection models (L. monocytogenes and S. typhimurium), a polyclonal subset of effector and cm-like уδ T cells release IFNy or IL-17 within 24 hours in an innate-like response. The naïve population however did not respond in this immediate fashion.

To accompany the murine results, I investigated the human Vδ1 уδ subset in lymphoid tissue and detected greater numbers of naïve cells in the tonsil than blood. The tonsil also had cm-like and effector populations, corresponding with murine subsets. The phenotypic characterisation of the populations aligned with murine cells, however human effector and cm-like cells showed clonal expansions in their TCR repertoire.

This thesis includes a thorough characterisation and comparison of adaptive-like populations in both mice and humans. This will help in shaping our understanding of the immunological role of these cells and guide future research in the field.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Immunology and Immunotherapy
Funders: Wellcome Trust
Subjects: Q Science > Q Science (General)
Q Science > QM Human anatomy
URI: http://etheses.bham.ac.uk/id/eprint/12265


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