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Title: Imprint of cytomegalovirus and varicella zoster virus infections on the immune system of healthy and diseased subjects
Author: Alejenef, Ali
ISNI:       0000 0004 2746 0402
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2013
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Primary infection with both cytomegalovirus (CMV) and varicella zoster virus (VZV) usually occurs at an early age, followed by lifelong persistent infection (latency phase). Indeed, frequent reactivation of latent viruses, particularly CMV, can be a major burden to the immune system and can play a role in configuration of the immune system. This thesis set out with the aim of understanding the balance between different arms of the immune system and CMV and also to find out the impact of immune modulation by this virus on the sequelae of coincident coronary artery disease (CAD). Meanwhile, the purpose of the VZV study was to determine the importance of adaptive immunity in protection against VZV reactivation in children with acute lymphocytic leukaemia receiving chemotherapy. The most obvious finding of the current CMV study is that the CMV-seropositive cohort exhibited a remarkable increase in the frequencies of CD28low CD4+, CD28low CD8+ T cells, NKG2Cpos NK Cells and Vδ2neg γδ T cells compared to CMV-seronegative donors. Furthermore, it shows that the expansion of Vδ2neg γδ T cells in CMV carriers is age related and does not correlate with changes in the magnitude of CMV-specific CD4+ or CD8+ T cell frequencies within those individuals. Phenotypically, Vδ2neg γδ T cells were found to be highly differentiated effector memory cells and did not possess ex vivo immediate effector function. In the CAD study, the most striking observation was the differences between AMI (acute myocardial infarction) and PMI (stable post myocardial infarction) patients in term of the distributions of polyfunctional CMV-specific CD4+ T cells that were characterized by the absence of IFNγ but expression of IL-2 plus any other measured functions (i.e CD107a, MIP1β, and/or TNFα). This cell subset was significantly increased in the PMI group. Finally, one of the more significant findings to emerge from the VZV study was the significant reduction in the absolute counts of VZV-specific IFNγ+ CD4 T cells and inversion of the VZV-specific CD4:CD8 (IFNγ producer) T cell ratio in those leukaemic children who developed clinical VZV infection. Contrasting with T cell responses, VZV-specific IgG was detected post primary infection in most patients; however, there was no clear association between the VZV-specific IgG antibody titre and VZV reactivation.
Supervisor: Christmas, Steve; Flanagan, Brian Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available