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Title: The immunomodulatory mechanisms of extracorporeal photopheresis
Author: Bladon, John
ISNI:       0000 0001 3466 7303
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2003
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Extracorporeal photopheresis (ECP) was originally pioneered as a treatment for Cutaneous T cell Lymphoma (CTCL) (Edelson et al., 1987). More recently, ECP therapy has been found to be effective in Graft versus Host Disease (GvHD) (Owsianowski et al, 1994). ECP involves the separation and exposure of leucocytes to 8-Methoxypsoralen (8-MOP) and UVA, treated cells are subsequently re-infused (Edelson et al., 1987). Lymphocytes demonstrating apoptotic markers are observed very early in the ECP process, immediately prior to re-infusion. The early apoptotic lymphocytes display phosphatidylserine externalisation, depolarisation of the mitochondrial membrane potential and a fall in Bcl-2/Bax ratio. Subsequent changes included the activation of the caspase cascade and expression of Fas-Ligand, observed 24 hours post ECP. The apoptotic lymphocytes are phagocytosed by monocytes following ECP. ECP-treated monocytes, unlike other UV therapies, retain the co-stimulatory markers necessary for the effective presentation of processed antigens. Immediately following ECP, the number of T-cells expressing TNFα and IFNγ falls, whilst levels of monocytes expressing TNFα are also reduced. The anti-clonotypic immunomodulatory response, thought to be induced by ECP (Edelson et al, 1994), may therefore be induced by the extensive immediate and progressive immunological challenge of infused apoptotic lymphocytes. This process is thought capable of removing the expanded malignant and autoreactive T cell clones present in patients treated using ECP (Edelson et al, 1994). In addition, down-regulation of TNFα and IFNγ may benefit the T-cell mediated conditions where these cytokines play a pathological role.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Apoptosis