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The role of reactive oxygen species in lymphocyte activation

Tatla, S; (1996) The role of reactive oxygen species in lymphocyte activation. Doctoral thesis , University of London. Green open access

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Abstract

The exact nature of the biochemical events which follow T cell antigen recognition, in conjunction with the appropriate major histocompatibility complex, still remains incompletely understood. It is well documented that oxygen free radicals are capable of oxidising various biological molecules leading to cellular alterations and if present in sufficient amounts, ultimately to cell death. Recently it has been suggested that smaller fluxes contribute to T cell effector functions. The aim of the work was to study the role of reactive oxygen species (ROS) in T cell activation. The effect of various stimuli (phorbol esterOPMA, calcium ionophoreoA23187, monoclonal antibodies, anti-CD3, anti-CD28 and anti-CD2) on three lymphocyte functions, ie. thymidine incorporation (measure of lymphocyte proliferation), IL-2 release and ROS production were analysed. Thymidine incorporation and EL-2 release were measured 48 hours after the addition of stimuli. ROS production was measured using the free radical sensitive dye 2'7'-dichlorofluorescein by flow cytometry. ROS fluxes, subsequent IL-2 release and proliferation were compared. The relationship between ROS and all responses was further examined using ROS scavengers (desferrioxamine, ascorbic acid, N-acetyl cysteine, vitamin E and DMSO) known to have differing modes of action. The concentration of antioxidant needed to block the enhancement of ROS production was compared to that needed to inhibit proliferation and IL-2 release by a similar degree. The data suggest that the generation of ROS can be dissociated from the subsequent events of T cell activation, and provides support for the hypothesis that the redox status of the cell and not the free radicals themselves are the crucial factor determining gene activity in these cells.

Type: Thesis (Doctoral)
Title: The role of reactive oxygen species in lymphocyte activation
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1514508
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