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Title: Regulation of cutaneous T cell apoptosis and its relevance to chronic inflammatory skin disease
Author: Orteu, Catherine Helene
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1999
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Animal and in vitro studies suggest that resolution of inflammation is largely dependant on the clearance of activated T cells by apoptosis (programmed cell death). This study has sought to confirm this hypothesis in vivo in humans. Cutaneous PPD-induced delayed type hypersensitivity (DTH) responses were investigated in healthy volunteers, to determine features associated with both the generation and resolution of the reaction. This resolving immunological reaction was then compared to untreated chronic lesional atopic eczema (AE), to investigate whether a reduction in T cell apoptosis is involved in the generation of chronic cutaneous inflammation. We have shown that in the DTH response, the induction phase involves not only recruitment, but also proliferation of CD4+ CD45RO+ T cells, while resolution occurs in part by induction of T cell apoptosis. Different waves of expression occurred in the two recognised groups of anti-apoptotic cytokines, at the height (IL-2R [gamma] chain family) and during the resolution phase (IFN-[beta]) respectively. We hypothesise that the proliferative phase and the resolution of the response are controlled by different levels of IL-2R [ ] chain cytokines, the presence of which promotes proliferation, while the absence of these mediators leads to apoptosis. Increased IFN-[beta] production during the resolution phase may allow the survival of a proportion of primed T cells destined to maintain specific memory. In chronic AE the distribution and phenotypic characteristics of infiltrating T cells were similar to those in resolving DTH responses, but low levels of T cell apoptosis were observed. IL-15 and IFN- [beta], members of both groups of anti-apoptotic cytokines, were expressed concomitantly. This may not only promote T cell recruitment and proliferation, but also cause excess numbers of T cells to survive in a state in which they can subsequently be reactivated without dying, and therefore contribute further to the cutaneous inflammatory response.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available