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BACKGROUND: Accumulating evidence suggests that T cells play an important role in the pathogenesis of atopic dermatitis (AD); yet, little is known of the differentiation status of CD4+ T cells specific for common environmental allergens, such as the major cat allergen, Fel d 1. OBJECTIVE: To determine the frequency, differentiation phenotype and function of circulating Fel d 1-specific CD4+ T cells in adult individuals with severe persistent AD in comparison with healthy controls. METHODS: Using HLA class II tetrameric complexes based on a HLA-DPB1*0401-restricted Fel d 1 epitope, ex vivo and cultured T cell frequency and phenotype were analysed in individuals with AD and healthy controls. Cytokine secretion was measured by ex vivo and cultured IL-4 and IFN-γ ELISpots. RESULTS: Ex vivo Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopics and non-atopics express high levels of CCR7, CD62L, CD27 and CD28, placing the cells largely within the central memory subgroup. However, the functional phenotype was distinct, with greater IL-4 production from the cells derived from atopics, which correlated with disease severity. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopic and non-atopic donors maintain a central memory phenotype; however in atopics, the cells had greater Th2 effector function, compatible with a disease model of altered antigen delivery in atopic individuals.

Original publication

DOI

10.1111/j.1365-2222.2011.03819.x

Type

Journal article

Journal

Clin Exp Allergy

Publication Date

11/2011

Volume

41

Pages

1555 - 1567

Keywords

Adult, Aged, Aged, 80 and over, Allergens, Animals, CD4-Positive T-Lymphocytes, Cats, Cell Line, Dermatitis, Atopic, Epitopes, T-Lymphocyte, Female, Glycoproteins, HLA-DP beta-Chains, Humans, Hypersensitivity, Immediate, Immunoglobulin E, Immunophenotyping, Male, Middle Aged, Peptides, Phenotype, Protein Multimerization, Young Adult