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Title: Role of accessory cells in cell-mediated immune responses in vitro, as studied using macrophage-active agents
Author: Lancaster, Fiona Caroline
Awarding Body: University of London
Current Institution: Imperial College London
Date of Award: 1987
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Two culture systems were used to study cell-mediated immune responses in vitro, namely the generation of murine alloreactive cytotoxic T lymphocytes, and the expression of non-specific spontaneous cytotoxic activity by cultured human peripheral blood mononuclear cells. Optimal culture conditions were determined for each system, and the role played by macrophage-like accessory cells was examined using cell depletion and separation techniques based on the adherent properties of these cells. In the mouse system, the adherent population was found to have a dual role, acting as allogeneic stimulator cells and providing an accessory function; in the latter capacity, there appeared to be no requirement for histocompatibility between the responder cells and the accessory population. In contrast, removal of the adherent fraction from cultures of human mononuclear cells resulted in increased cytotoxic activity, depending on the interval between adherent cell depletion and assay, and it is suggested that the effector cells in this system are undergoing a continuous process of maturation, which is regulated by the adherent population. Both Systems were further investigated by the addition of some known macrophage-active agents. The results obtained with silica were consistent with the hypothesis' that this material destroys phagocytic cells. Carrageenan and zymosan suppressed cell-mediated cytotoxicity in both culture systems, apparently acting via the accessory population without causing the death of such cells. Addition of latex beads to the cultures did not affect cytotoxicity. The role of cyclo-oxygenase metabolites of polyunsaturated fatty acids in mediating carrageenan- and zymosan-induced suppression was investigated using exogenous prostaglandin E1 and prostacyclin, together with antisera against these compounds. In the mouse system, the drugs indomethacin and flurbiprofen were also studied, and evidence is presented that cyclo-oxygenase products, particularly prostaglandins of the E series, are involved in regulating the generation of cytotoxic effector cells in vitro.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available