title: Allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis.
abstract: The majority of allergen-specific T cells derived from inhalant allergen patch test lesions in patients with atopic dermatitis were previously found to produce a restricted type-2 cytokine pattern. Recent studies, however, have revealed that in chronic eczematous skin lesions of patients with atopic dermatitis, expression of the type-1 cytokine interferon-gamma predominates. To evaluate cytokine production by allergen-specific T cells in chronic atopic dermatitis, we established house dust mite (Dermatophagoides pteronyssinus)-specific T-cell clones from the dermis of chronic skin lesions of sensitized adult patients with atopic dermatitis. Frequencies of skin-derived T cells proliferating in the presence of Dermatophagoides pteronyssinus were between one in 138 and one in 4255, indicating that only a minority of skin-infiltrating T cells are allergen specific. When these cells were analyzed for their capacity to produce interferon-gamma, the majority (71%) of these cells were found to express interferon-gamma mRNA and to secrete interferon-gamma protein, either alone or in combination with interleukin-4. Phenotypic analysis revealed that 15% of skin-infiltrating allergen-specific T cells were CD8+. No selection of Vbeta elements was detected in Dermatophagoides pteronyssinus-specific T-cell clones. These studies demonstrate that allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in lesional atopic dermatitis. The notion that the majority of allergen-specific, skin-infiltrating T cells are capable of producing interferon-gamma further supports the concept that interferon-gamma expression has major pathogenetic relevance for the chronic phase of atopic dermatitis.
authors.affiliation: Department of Dermatology, Hannover Medical School, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Werfel
authors.forename: A
authors.initials: A
authors.lastname: Morita
authors.forename: M
authors.initials: M
authors.lastname: Grewe
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: U
authors.initials: U
authors.lastname: Wahn
authors.forename: J
authors.initials: J
authors.lastname: Krutmann
authors.forename: A
authors.initials: A
authors.lastname: Kapp
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D000818:Animals; D003876:Dermatitis, Atopic / Q000276:immunology*; D004391:Dust; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008925:Mites / Q000276:immunology*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
chemical_list: D000485:Allergens; D004391:Dust; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma