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Title: Bystander T cell activation
Author: Bangs, Sarah Christine
ISNI:       0000 0001 3442 5187
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2007
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T cell responses are subject to several layers of regulation in order to prevent a detrimental effect on the host. Bystander T cell activation occurs via TCR-independent mechanisms, and as such evades certain control checkpoints. The apparent irrationality of this concept, coupled with the finding that the overwhelming majority ofT cells activated during viral infection are antigen-specific, has lead to a debate over the existence of the phenomenon. In this study, I sought to build upon previous work with murine models, to demonstrate the existence of bystander T cell activation in primary human T cells following initial stimulation of a distinct population of antigen-specific T cells with staphylococcal enterotoxin B (SEB). Furthermore, it has been established that this occurs in the absence of any opportunity for TCR cross-reactivity. Further investigation was made into the mechanism of activation, and the phenotype and function of bystander activated T cells. Phenotypic analysis indicated that bystander T cell activation in the SEB system occurred preferentially within a particular T cell subset. Distinct characteristics were identified amongst directly activated T cells and bystander activated T cells. The functional outcome with regards to proliferative capacity, apoptosis induction, and suppression by regulatory T cells was also investigated, Microarray analysis of resting, bystander, and directly activated T cells revealed distinct gene expression profiles, and analysis of differentially expressed genes supported an absence of TCR stimulation within the bystander population. Data furthermore indicated distinct mechanisms of apoptosis for bystander and directly activated T cells. Candidate cytokines implicated by the data were followed up with neutralisation assays. Taken together, the data support the hypothesis that bystander T cell activation induces a partial activation state in a proportion of memory T cells, which is followed by apoptosis, which may provide immunological space for newly generated antigen-specific memory T cells, while eroding pre-existing memory populations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available