McLarnon, Andrew (2011)
Ph.D. thesis, University of Birmingham.
Allogeneic stem cell transplantation is associated with a powerful T cell-mediated ‘graft-versus-leukaemia’ (GvL) effect and also ‘graft-versus-host disease’ (GvHD). Developing therapies to improve survival relies on greater understanding of these responses in order to enhance GvL and suppress GvHD. To gain an increased understanding of the mechanisms of GvHD I measured frequencies of Th1, Th17 and Treg subsets in the blood of 32 GvHD patients (during and outside of disease episodes) and in 21 patients who did not suffer GvHD. No associations between T cell subset frequencies or serum cytokine concentrations and incidence of GvHD were evident. My GvL work addressed whether T cell responses to cancer/testis antigens (CTAg) could be detected in a cohort of 41 patients who had undergone allogeneic stem cell transplantation for the management of acute myeloid leukaemia and multiple myeloma. CTAg-specific CD8+ T cell immune responses were observed within peripheral blood of five patients, with an average magnitude of 0.045% of the CD8+ T cell repertoire. T cell immunity was focussed against peptides derived from MAGE proteins and was increased within the bone marrow. These immune responses are likely to contribute to tumour eradication following transplantation and represent a potential novel mechanism for GvL.
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