Yang, D.S.-F.; (2012) Immunomodulatory effects of interferon-alpha on T cell subsets in Behcet’s disease ex vivo, and the in vitro effects of treatment on healthy donor cells. Doctoral thesis , UCL (University College London).

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Abstract

Many patients with Behcet’s disease (BD) have disease that is severe and do not respond to the conventional treatment of systemic corticosteroids and immunosuppressive agents. Recently, IFN-α therapy has shown promise as an effective treatment that may also improve long-term outcome. This study aims to provide an insight into the mechanisms of action and disease-modifying ability of IFN-α by focussing on the impact on T cell subsets. In this study, I describe my investigation into the effects of an additional 6-month course of IFN-α therapy in modulating T cell subsets and their cytokine expression in BD patients ex vivo over the first 12 months. Investigation of T cell responses confirms previous findings on Th1 and Th2 cells and their associated cytokines following IFN-α treatment. Analysis of Th17 cells shows these cells are downregulated by IFN-α therapy in peripheral blood. On the other hand, Foxp3+ T cells are upregulated by IFN-α therapy which is a novel mechanism that may contribute substantially towards the disease-modifying ability of IFN-α treatment. Notably, most effects of IFN-α on T cells, including Th17 and Treg cells, persist even after cessation of treatment. Also, I report in details the responses of CD4+, CD8+ and γδ T cell subsets in vitro following treatment of healthy donor PBMCs with IFN-α. The findings are largely in agreement with the ex vivo study. Fopx3-expressing and IFN-γ-, IL-10-, and TGF-β- producing CD4+ and CD8+ T cells are all increased by IFN-α treatment. Whereas, IL-17-producing CD4+, CD8+ and γδ T cell are decreased following treatment with IFN-α. Our data may provide new inroads into elucidating the immunomodulatory mechanisms involved in the disease-modifying ability of IFN-α therapy. Which of the above mechanisms plays the most important role in the observed beneficial effects of IFN-α in the treatment of BD remains to be elucidated.

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