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Title: Characterising lymphocyte subpopulations and heat shock protein 70 expression in clinical and experimental pulmonary arterial hypertension
Author: Shepherd, Amy
ISNI:       0000 0004 2735 8969
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2012
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Pulmonary arterial hypertension (PAH) is fatal disease of the small pulmonary arteries which is characterised by medial hypertrophy causing an increase in pulmonary vascular resistance and pulmonary artery pressure resulting in right ventricular failure and death. The pathogenesis of PAH has not been fully elucidated to date and there is no current curable pharmacological treatment. Inflammation is thought to play an important role in the pathogenesis of PAH. The work undertaken in this thesis aimed to investigate the role of T cells in the pathogenesis of PAH by characterising lymphocyte subsets (T and B cell distribution) in treatment-naïve patients with PAH and animal models of disease. I found that the relative frequency of CD8+ cytotoxic T cells in treatment-naïve Scleroderma associated-PAH patients was significantly decreased compared to corresponding controls. A negative correlation was also noted between the relative frequency of CD4+ T cells and several clinical parameters. To investigate cause or effect of changes in T cell frequency, I examined a time course of the paigen diet-fed ApoE-/-/IL-1R1-/- mouse model of PAH, but noted no difference in circulating T cell subset distribution. CD4+ T cell depletion rendered these animals more susceptible to the development of PAH. Collectively, these findings suggest that subtypes of PAH are associated with distinct T cell profiles. Alterations in circulating T cell and B cell subsets in clinical PAH, particularly CD8+ T cells suggest a dysfunctional immune system which could contribute to disease pathogenesis. In experimental models, the propagation of disease progression by depletion of CD4+ T cells suggests an anti-inflammatory nature of these cells within this disease setting. Future studies are needed to fully understand the exact role that T cells play in the pathogenesis of PAH.
Supervisor: Lawrie, Allan ; Pockley, Graham Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available