Craston, Rose Margaret Isabel; (2001) Cellular mediators of anti-leukaemic activity. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The aim of this project was to study the cells which mediate allogeneic and autologous anti-leukaemic activity. By studying blood samples from patients pre and post bone marrow transplant (BMT) we hoped to establish which cells played an important role in the post-transplant period. Phenotyping analysis was performed on patient samples from one month post-transplant for up to twelve months. From studying the results of the phenotyping data we have acquired a bank of data on immune reconstitution and constructed a hypothesis about possible mediators of graft-versus-leukaemia (GvL). Patient material was gathered at presentation and each month post-transplant. Cytotoxicity assays were performed by a flow cytometric method using patient material. Some of these experiments were performed on patients who had received chemotherapy and gone into remission, others had received autologous transplants. From these experiments it became apparent that a level of killing of around 17% was required to allow likelihood of survival and a subset of natural killer (NK) cells (CD56+/CD8+) was identified and appeared to have specific anti-leukaemic potential after autologous BMT. This subset has been studied extensively in terms of its biology. Both CD3-/CD56+/CD8+ and CD3-/CD56+/CD8- subsets were monitored to see if they reacted in different ways to cytokine stimulus and to discover whether they had similar cytotoxic potential. Three different cytokines were employed to generate ex vivo expansion of these cells from their precursors. Interleukin 2 (IL-2), interleukin-7 (IL-7) and interleukin 15 (IL-15) were used separately and in combination in an attempt to establish what their role was in the development of NK cells and the survival of NK cells in vitro.

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