Investigation of T cell responses in multiple sclerosis

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Al Mulhim, Muneera (2020). Investigation of T cell responses in multiple sclerosis. University of Birmingham. Ph.D.

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Abstract

Multiple myelin proteins, including myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and myelin proteolipid protein (PLP), are critical T cell autoantigens in multiple sclerosis (MS). However, the contribution of these autoreactive T cells to disease pathology remains unknown. We identified CCR6+ CD4+ myelin-reactive T cells in the peripheral blood of healthy controls where they produced low levels of inflammatory and regulatory cytokines. CCR6+ myelin reactive T cells from patients with untreated MS exhibited significantly enhanced production of interferon-γ (IFN-γ), interleukin-17 (IL-17), granulocytemacrophage colony- stimulating factor (GM-CSF) and Tumor necrosis factor-α (TNFα) compared to healthy controls. However, IL-10 expression was less abundant in healthy controls when compared to untreated MS patients, suggesting a role for IL-10 in regulating the pathology of MS when there is inflammation. Interestingly, the proinflammatory profile of CCR6+ myelin reactive T cells including GM-CSF, IFN-γ, IL17 and TNF-α were higher in MS patients treated with IFN-β. Our data suggest that despite the impact of IFN-β on reducing relapse rates in MS, there is little impact on the frequency of pro-inflammatory cytokine secreting autoantigenspecific CCR6+ CD4+ T cells. It remains to be established if the increased proinflammatory cytokine production is present early during the disease.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):