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Title: The role of BCL6b and CD27 in the clonal expansion of CD8+T cells without effector differentiation
Author: Carr, J. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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It has been proposed that a self-renewing, “stem-cell” like stage of CD8+ T cell development exists in which a potential for proliferation and clonal expansion is maintained without effector differentiation. The possibility that the transcriptional repressor BCL6b, or costimulation via a receptor of the tumour necrosis factor superfamily of proteins, was responsible for allowing the expansion of CD8+ T cells without the development of effector properties was assessed.  This study demonstrates that BCL6b partially blocked the IL-2 induced increase in CD8+ T cell numbers and upregulation of the IL-2-regulated gene CD25 in vitro, but was unable to show an ability of this transcription of the IL-2-regulated gene CD25 in vitro, but was unable to show an ability of this transcription factor to prevent IL-2-mediated effector differentiation.  Additionally, CD27 was identified as the costimulatory receptor which, in combination with T cell receptor (TCR) signals and the pro-survival cytokine IL-7, drives the IL-2-independent clonal expansion of CD8+ T cells. CD27 was shown to enhance TCR induced cells cycling and to maintain the expression of the IL-7 receptor. Importantly, cells stimulated via the TCR and CD27 did not acquire effector functions and were capable of subsequently expanding and differentiating in response to a viral challenge in vivo. Therefore, a pathway of CD8+ T cell clonal expansion that maintains the IL-7 receptor, is not associated with effector differentiation and preserves the potential of the cell for further clonal expansion and the development of effector functions has been defined, lending evidence to the existence of a “stem-cell” like population of CD8+ T cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available