Allergic diseases such as asthma and atopic dermatitis (AD) are a major public health concern. Though a role for CD4+ T cells is well recognized in IgE-mediated disorders, the properties and function of these cells and the relationship to development of IgE responses and allergic inflammation remains enigmatic. A population of skin-homing CD4+ T cells which express high levels of CD25 (IL-2R
In Aim 2, combined cross-sectional and longitudinal studies in children (ages 0 to 17 years) with AD will be used to identify novel markers of disease progression and severity. Changes in discrete subsets of circulating CD25+CD4+ T cells associated with nascent and maturing IgE ab responses will be monitored by flow cytometry. The kinetics of IgE responses and production of pro-inflammatory cytokines/chemokines, including the CCR4-promoting chemokine, CCL17/TARC, will be assessed in parallel by multiplex cytometric bead assay.
In Aim 3, cytokine/chemokine genes which are differentially expressed by CD25+CCR4+ T cells from asthmatic versus AD patients will be analyzed using microarray techniques. Antigens identified will be used as markers to monitor changes in circulating CD25+CCR4+ T cells isolated from asthmatic patients during an anti-lgE treatment regimen by flow cytometry. As an adjunct to these studies, the effect of experimental rhinovirus challenge on these cells and the relation to clinical disease will be assessed based on objective measures of lung function and inflammation. Studies in Aims 2 and 3 are pivotal to defining the relationship between discrete functional T cell subsets, IgE and allergic inflammatory processes. Public Health: Defining """"""""pro-allergic"""""""" T cells and their link to IgE could provide new targets for therapy.
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