Kalra, Seema (2017) Characterisation of pathogenic T helper and T regulatory cell subsets in relapse and progression in multiple sclerosis. Doctoral thesis, Keele University.

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Abstract

Multiple Sclerosis (MS) is one of the commonest disabling neurological diseases affecting the young in the developed world. It affects the central nervous system (CNS) and is characterised by inflammation with neuronal demyelination /degeneration and failure of remyeli nation/regeneration.

Inflammation is present throughout the course of the disease though it differs qualitatively and/or quantitatively in different phases. T cells are the central players in the immune processes and more so in an autoimmune disease like MS. Autopsy studies continue to add to our understanding of CNS inflammation.

I studied the role of pathogenic and regulatory T cells in MS. I have demonstrated that there is a peripheral immune dysregulation as seen in some previous studies involving the Th17 cell axis. I observed the presence of raised frequencies of non-classic Th1 cells and dual positive Th17-Th1 cells in MS. Dual expression IL-17+1L-22+ cells were also raised in MS. Results included raised frequencies of Th22 cells in the blood in MS. This suggests the role of Th22 in pathogenesis of MS. The chemokine receptor CCR6 is considered Th 17 lineage associated. I noted the expression of CCR6 not only on Th 17 cells, but also on Th1, Th22 and Th21 which alludes to the role of these cells in causing CNS inflammation via the entry into the CNS though CCR6-CCL20 trafficking axis.

I observed reduced frequencies of CTLA-4+ T cells which points to their limited regulatory capacity in MS. These findings provide important clues towards the pathogenesis of MS. These findings however, do not correlate with the disease activity and disease severity of MS at this stage .. The plan is to explore the clinical correlation and contribution of these findings in the pathogenesis of the disease in further studies.

Item Type: Thesis (Doctoral)
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Lisa Bailey
Date Deposited: 13 Nov 2017 16:33
Last Modified: 13 Nov 2017 16:33
URI: http://eprints.keele.ac.uk/id/eprint/4215

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