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Title: Investigation of the impact of CD4+CD25+ regulatory T cells on immune responses induced in vivo
Author: Richards, Hannah Elizabeth
ISNI:       0000 0004 2750 5631
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2007
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CD4+CD25+ regulatory T cells (Treg) are known to inhibit T cell responses however their site of action and whether they suppress other immune responses has not been well characterised. Using a model of tumour rejection involving a melanoma cell line expressing Fas ligand (B16FasL) the effect of Treg on these responses has been studied. NK cells and macrophages were found to play a critical role in rejection of B16FasL. Depletion of Treg enhanced tumour rejection, whilst adoptive transfer of Treg inhibited tumour rejection, indicating that Treg suppress innate immune responses. Experiments performed to identify the Treg target indicated that Treg inhibit the cytolytic activity of NK cells. Furthermore, depletion of Treg enhanced the inflammatory infiltrate within 24 hours, which consisted of elevated numbers of neutrophils, indicating that Treg not only inhibit innate immune responses, but also act rapidly. Another aim of this project was to identify whether Treg act in lymphoid organs or at the tumour site. T cells from transgenic mice, in which lymph node horning receptor CD62L expression is maintained upon activation (LAP), were predicted not to enter inflamed tissue. However, experiments showed that T cells from LAP mice could enter inflamed lungs following influenza infection. Characterisation of memory T cell responses indicated that LAP mice exhibit delayed viral clearance, despite comparable cell numbers, cytolytic activity, and levels of CD 107a and IFNy. Control transgenic mice in which CD62L can be shed, showed no defect in viral clearance indicating that inability to shed CD62L in LAP mice did not affect T cell migration but compromised anti-viral immunity. Although not suitable to study location of Treg action, this data indicated that CD62L shedding is important for memory T cell responses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available