Zhang, Xiaozhe; (2019) The Role of Immune Regulatory Cells in Sight-threatening Non-infectious Uveitis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Non-infectious uveitis is a clinically heterogeneous disease which can cause severe vision loss. Studies have shown T regulatory cells (Tregs) and B regulatory cells (Bregs) participate in the immune regulation of immune-mediated diseases such as uveitis, and uveitis can be influenced by environmental factors such as changes to the gut microbiome. This study aims to provide an insight into the immune regulatory mechanisms of non-infectious uveitis by focusing on regulatory cells. The first study investigated the long-term effect of pegylated interferon-α-2b therapy on Tregs in patients with Behçet’s disease and an associated uveitis. At 24 months, no difference was found in terms of clinical outcomes between patients on standard treatment and those on peginterferon-α-2b therapy in addition to standard treatment. The frequency of Tregs, which increased at 3, 6 and 12 months, decreased at 24 months in peginterferon-α-2b group. The IL-10 level in cell culture supernatants was elevated at 6 months in peginterferon-α-2b group. The second study included 50 idiopathic uveitis patients and 10 healthy individuals. Clinical remission of uveitis was associated with a higher level of Bregs in peripheral blood, and the capability of Bregs in suppressing proliferation of effector T cells. IL-10 levels in sera were significantly higher in inactive patients compared to active patients, and lower in active patients compared to controls. In the third study, experimental autoimmune uveitis (EAU) was induced in mice. The frequency and IL-10 expression of different Breg subsets, including B10, transitional 2-marginal zone precursors, marginal zone B cells, and B-1 cells, were associated with clinical severity, which was influenced by depletion of the gut microbiome and changes in housing conditions. The isolated B10 cells suppressed pathogenic T cell proliferation. Preliminary results also demonstrated a correlation between the effect of topical dexamethasone treatment in reducing EAU severity and increasing levels of Bregs.

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