An investigation of T lymphocyte migration induced by CD44 activation
Citation:
Áine Fanning, 'An investigation of T lymphocyte migration induced by CD44 activation', [thesis], Trinity College (Dublin, Ireland). School of Medicine. Discipline of Clinical Medicine, 2006, pp 286Download Item:
Abstract:
This thesis investigates the role of CD44 in signalling active migration in T lymphocytes. A number of murine studies have demonstrated that loss of CD44 expression by T lymphocytes resulted in a delayed migration to sites of inflammation. However, migration to lymph nodes was normal (Camp et al., 1993; Stoop et al., 2002), suggesting that this adhesion receptor is required for T cell migration under inflammatory conditions. In this study, the responses of human T cells following cross-linking of CD44 were examined. Engagement of the CD44 receptor using immobilised monoclonal antibody induced cytoskeletal rearrangement and cell polarisation. Further analysis demonstrated that these changes in morphology were accompanied by active migration. Further investigation was carried out using pharmacological inhibitors to determine the signal-transduction pathways switched on following engagement of CD44. In particular, the roles of protein kinase C (PKC) isoforms and the lipid kinase, phosphoinositide 3-kinase (PI3-kinase) were examined. Go6976, a selective inhibitor of classical PKC isozymes, suppressed lymphocyte polarisation and migration following CD44 ligation. However, selective inhibition of PKC5, using rottlerin, reduced CD44- activated migration but did not completely ablate it. Two inhibitors of PI3-kinase were used to examine the role of this lipid kinase in CD44-induced migration. The competitive inhibitor, Ly294,002, suppressed lymphocyte polarisation. However, wortmannin did not significantly alter lymphocyte morphology in response to CD44 engagement.
Author: Fanning, Áine
Advisor:
Kelleher, DermotQualification name:
Doctor of Philosophy (Ph.D.)Publisher:
Trinity College (Dublin, Ireland). School of Medicine. Discipline of Clinical MedicineNote:
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