Varey, Anne-Marie; (1991) Regulation of the immune response studied in vitro. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In an attempt to study the regulation of the immune response in vitro, different agents have been used. Some appear to affect proliferation and/or differentiation of B cells and some specifically affect certain T cell subsets. Infection with pseudomonas aeruginosa is lethal m mice and the extracellular slime glycoprotein (GLP) has been identified as the pathogenic component. The effect of GLP on murine lymphocytes has been studied. GLP was shown to act like a B cell mitogen, in fact this could be described more specifically as a TI-2 polysaccharide antigen and GLP also caused non-specific terminal differentiation of B cells into immunoglobulin secretion. Repeated injections of 2'-deoxyguanosine (dGuO) can mimic purine nucleoside phosphorylase deficiency, which manifests itself as a selective T cell dysfunction. Using systems where the simultaneous development of T suppressor and cytotoxic cells occur, dGuO partially abrogates suppression but leaves the cytotoxic component unaltered. No effect on different populations of cytotoxic cells could be demonstrated and antigen presentation to T cells also appeared unaffected. The effect of cyclosporin A (CsA) on antigen presentation to T cell lines and clones was investigated. Pre-pulsing the antigen presenting cells with CsA inhibited proliferation to the specific antigen and also prevented cytokine release by these T cell lines. The effect of CsA on T cell triggering via anti-CD3 or idiotypic antibody were also studied. Conflicting results were obtained with T cell lines or clones and T cell hybridomas. Using T cell lines developed in this laboratory, the release of cytokines spontaneously, or following antigenic stimulation, were studied. Following on from this, the effect of various purified cytokines on the T-independent autologous plaque forming (PFC) assay were investigated. The majority of these factors did not affect this response with the exception of IL-5 and BCDF (SJL(4)F) which were consistently shown to have an enhancing effect in this assay. One T cell line, SJL(4), was extensively studied in order to identify the factor(s) which could enhance the autologous PFC assay. A factor produced by SJL(4) cells, SJL(4)F, appears to be distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6 and IFN-γ and therefore may well be a BCDF as yet undescribed in the current literature.

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