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Title: An investigation of T cell dysregulation in B-cell chronic lymphocytic leukaemia
Author: Scrivener, Sophie Grace
ISNI:       0000 0001 3391 6320
Awarding Body: University of Plymouth
Current Institution: University of Plymouth
Date of Award: 2002
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B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by an accumulation of clonal malignant B cells within lymphoid tissue, the bone marrow and the peripheral blood. Whilst abnormalities of these B cells are the essential cause of this disease, the aim of this research project was to investigate whether the T cell compartment may play a role in the aetiology of this disease by evaluating the expression of key surface antigens involved in both activation of and interaction with B cells and other antigen presenting cells of the immune system. There were marked abnormalities in the expression of certain key activation and interaction antigens on the peripheral blood T cells of patients with BCLL, in particular, compared to normal controls, there was a significant reduction in the number of circulating T cells expressing CD25, CD28, CD152, CD4, CD5 and CDI Ia. There was no difference in expression of TCRccp, CD8, CD54 and CD154. Significantly more T cells from CLL patients expressed HLA-DR. Removal of the malignant clone of cells prior to short-term T cell culture did not affect expression of these markers. Numbers of T cells expressing intracellular CD25 and CD152 were not decreased after activation and a significantly greater number of resting T cells expressed both antigens intracellularly. There was also evidence of a soluble factor present in CLL AB serum which caused increased numbers of normal and CLL T cells to express CD25 and CD 152 after culture. Initial results suggest that this may be IFN-y, levels of which were significantly higher, as measured by ELISA, from resting CLL T cells compared to normals. By studying the expression of these antigens using cell culture, flow cytometric and ELISA techniques, the results suggest a functional state of anergy in these T cells. This anergic state may contribute to the pathogenesis of B-CLL and its related phenomena of immunosuppression and autoirnmunity. This was further reflected in the results of the T cell functional studies and reduced IL-2 expression in the mixed lymphocyte reaction (MLR).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Cancer Medicine Molecular biology Cytology Genetics