Croll, Andrew David (1986) The regulation of polyclonal mitogen-stimulated human gamma-interferon production. PhD thesis, University of Warwick.

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Abstract

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.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QP Physiology Q Science > QR Microbiology
Library of Congress Subject Headings (LCSH):	Leucocytes, Interferon, Interleukin-18, Peripheral circulation -- Regulation, Mitogens
Official Date:	September 1986
Dates:	Date Event September 1986 Submitted
Institution:	University of Warwick
Theses Department:	Department of Biological Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Morris, A. G. (Alan George)
Sponsors:	Cancer Research Campaign (Great Britain)
Extent:	1 volume (various pagings) : illustrations
Language:	eng

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