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 B-CLL,
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 CD11a.
There was no difference in expression of TCRαβ, 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 CD152
after culture. Initial results suggest that this may be IFN-γ, 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 autoimmunity. This was further reflected in the results of the T
cell functional studies and reduced IL-2 expression in the mixed lymphocyte reaction
(MLR).
Date of Award | 2003 |
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Original language | English |
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Awarding Institution | |
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An investigation of T cell dysregulation in B-cell chronic lymphocytic leukaemia
SCRIVENER, S. G. (Author). 2003
Student thesis: PhD