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Title: The role of EBV latent membrane protein 1 induced regulatory T-cells in latent infection and Hodgkin lymphoma
Author: Marshall, Neil A.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2006
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Healthy EBV seropositive donors tested for the ability to mount Th responses against LMP1 responded with secretion of high levels of the immunosuppressive cytokine IL-10 which was secreted from cells phenotypically analogous to the Tr1 class of regulatory T-cells.  The epitopes inducing this IL-10 secretion were clustered in the hydrophobic, transmembrane half of the protein that corresponded to a cluster of high affinity MHC class II binding domains.  Since the LMP1 induced TO cells could effectively suppress immune responses in an IL- 10 dependent manner, it seems likely that the induction of regulatory T-cells serves to prevent anti-EBV immune responses and aid viral persistence. PBMC and HLIL from HL patients also responded to stimulation with LMP1 by predominantly secreting IL-10.  However, these patients appeared to mount weaker responses compared to healthy donors.  In addition, a defect in their ability to mount Th1 responses against a range of control stimuli was documented.  HL patient HLIL were highly enriched for populations of both Tr1and CD4CD25 regulatory T-cells, which were strongly suppressive.  Such enriched populations of regulatory T-cells may be induced by LMP1 in EBV positive cases of HL and will act to prevent anti-tumour immune responses and aid tumour growth and persistence. Thus the Th cell response to LMP1 is dominated by the induction of regulatory T-cells in both latently infected donors and HL patients.  This strategy of induction of Tr cells should serve to protect EBV infected cells (either latently infected B-cells or H-RS cells) from clearance by the host.  This strategy of immune evasion via the induction of Tr cells may well be found with other persistent viral infections and tumours.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available