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Regulation of Dendritic cell function by the ocular microenvironment

Denniston, Alastair K O (2010)
Ph.D. thesis, University of Birmingham.

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The ocular microenvironment is immunosuppressive in animal models of antigen presenting cell function. My hypothesis was that in humans the normal ocular microenvironment maintains an immature dendritic cell (DC) phenotype, whereas in intraocular inflammation (uveitis) this regulation fails, permitting full DC maturation leading to the production and recruitment of pathogenic effector T cells to the eye. Using an in vitro model of DC function, I observed that non-inflammatory aqueous humour (AqH) inhibited DC maturation, with reduced MHC and CD86 expression, and reduced capacity to induce proliferation of allogeneic T cells, an effect which was cortisol and TGFβ2 dependent. In contrast, exposure to uveitis AqH generated a distinct DC profile with IFNγ dependent elevation of MHC class I, but reduced MHC class II and CD86 expression and impaired induction of T cell proliferation. Exposure to uveitis AqH from patients on topical glucocorticoid treatment caused additional suppression of CD86. Characterisation of ex vivo myeloid DC from patients with uveitis supported the findings of the in vitro model, with AqH-derived myeloid DC showing elevated MHC, but reduced CD86 expression. In summary human AqH is shown to be a powerful inhibitor of DC maturation, retaining this regulatory role during uveitis.

Type of Work:Ph.D. thesis.
Supervisor(s):Curnow, SJ and Murray, Phil I
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:RE Ophthalmology
Institution:University of Birmingham
ID Code:932
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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