Characterisation of cellular communication between an inflammatory site and the draining lymph node

Hayes, Alan James (2017) Characterisation of cellular communication between an inflammatory site and the draining lymph node. PhD thesis, University of Glasgow.

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In order to track cell migration, the project used a transgenic mouse system which ubiquitously expressed the fluorescent protein kaede that undergoes photo-conversion when exposed to violet or ultraviolet (UV) light. By inducing inflammation in peripheral tissues (e.g. the ear pinna on the hind footpad) and subsequently exposing the tissue to UV light, it was possible to spatiotemporally track the fate of the cells at these tissue sites. The study revealed that tissue resident cells do not constitute the majority of the migratory population and that immune cells must first be recruited to the site of challenge prior to migration. Migration from the site of challenge to the draining lymph node occurs within the first 48 hours post injection and returns to baseline over the following 24 hours. By combining the above approach with the YAe/Eα system to track antigen presentation, the study has also shown that antigen presentation persists for the first 24-36 hours and the majority of cells presenting antigen are CD103+CD11b+ dendritic cells. In collaboration with UCB, CyTOF profiling was performed on the migratory population to identify the diversity of these cells, identifying CD4+ T cells, CD8+ T cells, γδ T cells, B cell and neutrophils in the draining lymph node originating from the injection site.

Therefore, it is suggested that the migratory cells work in tandem with one another to control the initiation of adaptive immunity and determine the nature and the magnitude of the immune response. Additionally, the nature of an inflammatory stimulus can alter the magnitude and composition of the migratory population. This study highlights that our current knowledge regarding the initiation of adaptive immunity, in particular, the kinetics and phenotype of the migratory cells, remains limited. Further developing our understanding of the migratory population, antigen presentation and the kinetics of antigen presentation may help to identify new targets for immunomodulation for the treatment of inflammatory disorders or the development of new and improved vaccine adjuvants.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Cell migration, antigen presentation, immunology, spatiotemporal mapping, cell tracking, kaede, dendritic cell.
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Immunology & Infection
Supervisor's Name: Brewer, Professor James
Date of Award: 2017
Embargo Date: 10 May 2021
Depositing User: Mr Alan Hayes
Unique ID: glathesis:2017-8160
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 31 May 2017 11:56
Last Modified: 11 May 2020 09:03

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