Use this URL to cite or link to this record in EThOS:
Title: The regulation of polyclonal mitogen-stimulated human gamma-interferon production
Author: Croll, Andrew David
ISNI:       0000 0001 3397 1055
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 1986
Availability of Full Text:
Access from EThOS:
Access from Institution:
The regulation of human interferon-gamma production by peripheral blood mononuclear leukocytes, stimulated by polyclonal T-cell activators (mitogens), was investigated because of its possible importance as a regulator of the immune response and because it usually accompanies lymphocyte activation. Low density lymphocytes, enriched for large granular lymphocytes, were shown to be capable of IFN-gamma production in the absence of macrophages, unlike T-cells, but with interaction of two subsets of this low density population being required for optimal production. It is suggested that a non-T cell low density population can act as accessory cells for T-cells in the absence of macrophages. The action of both positive and negative modulators of IFN-gamma production were investigated. The importance of IL-1 production was demonstrated by the depressive effects of anti-IL-1 antibody and the ability of purified IL-1 to reverse the depressive effects of macrophage-depletion on T-cell activation. Blockade of the IL-2 receptor by monoclonal antibodies inhibits IFN-gamma production, as does treatment with prostaglandin E2, known to inhibit IL-2 production. The receptor blockade is reversible by pure IL-2 as is the PGE2 inhibition. IL-1 and IL-2 alone rarely induced any IFN-gamma. These data imply that for maximal IFN-gamma production the interaction of at least two other protein factors (IL-1, IL-2) with mitogen-stimulated T-cells is necessary, and that other factors may act as down-regulators. A variety of cell-surface molecules involved in MHC restriction and also the T11 antigen were also shown to have regulatory effects. Those of the T11 pathway may involve effects on calcium and IL-2 levels. T-cell activation could also be triggered by calcium ionophore plus tumour promoter. Activation of the IL-2 and IFN-gamma genes by this method was shown to be coordinate and not to require protein synthesis. Thus many regulatory effects on IFN-gamma production probably act at a post-transcriptional level.
Supervisor: Not available Sponsor: Cancer Research Campaign
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology ; QR Microbiology