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Title: Studies on the growth of Theileria infected bovine cells in immunodeficient mice
Author: Fell, A. H.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1990
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The experiments described in this thesis investigated the growth of bovine cells infected with Theileria sp. macroschizonts in various strains of immunodeficient mice. It was hoped that it would be possible to create a system for the growth of Theileria infected cells in vivo without using bovine hosts. Previous work had shown that T.parva infected cells would establish as subcutaneous tumours in irradiated Swiss and nude mice (Irvin et al, 1977; Veterinary Parasitology 3, p.141-160). Most of the work in this thesis concerned the related parasite, T.annulata. T.anmilata infected cells were found to grow as subcutaneous tumours in irradiated Balb/c, irradiated NIMR and Balb/c nude, and unirradiated C.B-17 scid (severe combined immunodeficiency) mice. Infected cells failed to establish in C57 beige mice, with or without irradiation. The growth and survival of the tumours was dependent on the degree of immunosuppression of the host, and the size of the cell dose administered. In Balb/c mice, T.annulata tumours regressed as mice recovered from irradiation. Analysis of lymphocyte subsets using a fluorescence-activated cell sorter (FACS) showed differential susceptibility of B-cells, T-helper and cytotoxic T-cells to a sublethal dose of ionising radiation (46y). The numbers of these lymphocytes increased more rapidly after irradiation in tumour bearing mice than in those without tumours. In irradiated (46y) Balb/c nude and scid mice, subcutaneous T.annulata tumours failed to regress, despite the development of general haemorrhage and central necrosis. In scid mice, high doses (2xl07) of T.annulata infected cells injected intraperitoneally gave rise to ascites. However, low doses (2xl06 cells) did not. The presence of macroschizont infected cells in the peritoneal cavity was accompanied by a proliferation of macrophages. Several lines of evidence indicated that natural killer (NK) cells were not effective against T.annulata-infected cells in scid mice, but that macrophages were capable of controlling and eliminating the cells, particularly in the peritoneal cavity. In all the strains of mice examined, subcutaneous T.annulata tumours appeared to be damaged by natural immune mechanisms (macrophages) and neutrophils leading to haemorrhage and necrosis. However, the ability of the mice to completely reject the tumours depended on the presence of T and B-cells. Tumour Necrosis (TNF) was not detected in serum, or in tumour extracts. Attempts to induce tumour rejection using a preparation of rabbit TNF were not successful. Attempts to affect the growth of r.annu/ato-infected cells, injected i/p into scid mice, with human alpha and gamma interferons (HulFN-g, were also unsuccessful. The neutralisation of endogenous murine IFN-g with a monoclonal antibody allowed increased growth of T.annulata and 7".parva-infected cells in the intraperi-toneal site in scid mice. Of the mouse strains examined, the scid mouse was the most favourable host for Theileria-infected cells. Attempts to establish uninfected bovine cells in scid mice were not successful, and these results cast doubt on the use of scid mice as hosts for uninfected cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available