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).
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.
|Title:||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|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology|
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