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Immune mechanisms in atopic eczema and the impact of therapy

Banerjee, Piu; (1999) Immune mechanisms in atopic eczema and the impact of therapy. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

Lesional skin in atopic eczema (AE) exhibits a T ceil dominated cellular infiltrate suggestive of a type IV hypersensitivity reaction. The T lymphocytes involved appear to be predominantly T helper type 2 cells. Raised IgE levels and positive prick test reactivity to aeroallergens are also commonly seen implicating involvement of allergic immediate type hypersensitivity. The presence of IgE receptors on antigen presenting cells may provide a link between these two mechanisms. In AE, the low affinity IgE receptor, FcγRII or CD23, is found in lesional skin to be largely expressed on Langerhans cells and dermal dendritic cells, that is those cells capable of antigen presentation. This study investigates the relevance of IgE receptors to the pathogenesis of AE in terms of cellular distribution and the regulation of their expression. Relationships between CD23 expression and clinical severity are revealed in the context of local immunological activity in the skin. A cohort of patients with AE were recruited and treated with Chinese herbal therapy (CHT) to test the relationship between immunological parameters and disease severity. Firstly it was established that treatment with CHT in this patient population resulted in an improvement in clinical disease. The distribution of IgE receptors on immunocompetent cells in lesional skin in AE and the emergence of these receptors during differentiation of cells of the monocyte/macrophage series were investigated. The relationship between T cell cytokine release and the level of egression of IgE receptors within the skin was determined. Using a standard clinical scoring system, it was confirmed that CHT improved the clinical status of patients in terms of reducing erythema and surface damage and the area of skin involved. Sequential use of immunoperoxidase and alkaline phosphatase-anti-alkaline-phosphatase immunohistological methods were employed to reveal the distribution of CD23 on mature cells in lesional skin. The results showed that as clinical severity was reduced, the numbers of CD23+ Langerhans cells and the numbers of CD23+ macrophages also decreased. Treatment also lead to a downregulation of the level of CD23 expressed by antigen presenting cells. To determine whether the changing proportions of CD23+ macrophage subsets in lesional skin resulted from dysfunction in monocyte differentiation, peripheral blood monocytes were isolated by adherence and cultured for 7 days. Immunocytochemical staining procedures were used to determine the relative proportions of emerging macrophage subsets and the distribution of CD23. Treatment did not affect the emergence of the RFD1+ inducer macrophage phenotype during the culture period however, there was a significant increase in the proportion of RFD7+ effector macrophages as compared to the situation before treatment. Interestingly, monocytes from patients with AE differentiated faster than those from normal controls but by day 7, the proportions of differentiated macrophages were similar. At day 0, therapy reduced the proportion of RFD1+ monocytes coexpressing CD23 however this difference was lost after 7 days of culture. Notably, throughout the 7-day culture period, larger proportions of monocytes from patients with AE were found to express CD23 compared with normal controls. To investigate aspects of T cell control of CD23 expression, methods of in situ hybridisation were performed on lesional skin before and after clinical improvement to identify the presence of mRNA for Interleukin-2 and Interleukin-4, (Th1 and Th2 type cytokines respectively). Following treatment, there was a decrease in the level of expression of mRNA for IL-4 and no significant change in the level of IL-2 mRNA. This study reveals an aberrant expression of CD23 on antigen presenting cells within lesional skin in AE and that treatment leading to clinical improvement results in a downregulation of CD23 expression. Therapy also leads to a decrease in Th2 activity as demonstrated by reduced IL-4 mRNA levels in the lesions, suggesting that this may also be relevant to the pathogenesis of AE. This research has thus revealed that CD23 expression by antigen presenting cells and local TH2 like T cell activity, is modulated by a course of therapy that improves clinical disease status.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Immune mechanisms in atopic eczema and the impact of therapy
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Antigen presenting cells
URI: https://discovery.ucl.ac.uk/id/eprint/10113805
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