L R Crack1, H W Chan, T McPherson, G S Ogg. 1. MRC Human Immunology Unit, University of Oxford, Weatherall Institute of Molecular Medicine, Oxford, UK.
Abstract
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.
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.
Authors: Karen A Smith; Nicola J Gray; Elizabeth Cheek; Femi Saleh; Jo Lavender; Anthony J Frew; Florian Kern; Michael D Tarzi Journal: BMC Immunol Date: 2013-03-22 Impact factor: 3.615
Authors: Karen A Smith; Nicola J Gray; Femi Saleh; Elizabeth Cheek; Anthony J Frew; Florian Kern; Michael D Tarzi Journal: BMC Immunol Date: 2013-11-05 Impact factor: 3.615
Authors: B Bonnet; K Messaoudi; F Jacomet; E Michaud; J L Fauquert; D Caillaud; B Evrard Journal: Allergy Asthma Clin Immunol Date: 2018-04-10 Impact factor: 3.406