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Title: Identification of interleukin-10 producing cells specific for Epstein-Barr virus latent membrane protein 1 and the involvement of interleukin-27 in their induction
Author: Forrester, Megan Amy
ISNI:       0000 0004 2721 8958
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2011
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During latent Epstein-Barr virus (EBV) infection, the T helper cell response to the EBV latent membrane protein (LMP)1 is dominated by the production of IL-10, but by IFN- γ during acute EBV infection. The purpose of this thesis was to develop methods for the enumeration and characterisation of the IL-10 producing CD4+ T cells that respond to peptides of the EBV protein LMP1, and to investigate the possible involvement of IL-27 in the development of these cells. It was found that some human donors have very high concentrations of IL-27 within serum, which is not dependent on EBV infection status but demonstrates relatively low heritability. The addition of IL-27 to cultures of human T cells did not induce IL-10 but the production of IL-17 was inhibited. To identify and characterise LMP1 responsive cells I used CD154 as a marker of activated T cells. Having optimised the methodology, 14 donors of known EBV serostatus were tested for activated IL-10 producing cells after culturing peripheral blood mononuclear cells with LMP1 peptides. However in most cases the frequency of CD4+ lymphocytes upregulating CD154 and IL-10 in response to LMP1 peptides was below the assay’s sensitivity. When the CD154+IL-10+ CD4+ cells were stained for T helper cell subset markers they were positive for every marker and isotype control, suggesting that the cells were non-specifically binding labelled antibody. Both single positive CD154+ and single positive IL-10+CD4+ cells were also present in response to LMP1, but again typically at frequencies below the level of sensitivity for this assay. The conclusions of the work are that IL-27 responses are heterogeneous, but unlikely to play an important role in the induction of IL-10+ T cells in EBV infection. The frequency of LMP1 responsive T cells is very low (<0.08%) in most donors.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Epstein-Barr virus ; Interleukins ; Interleukin-10