title: α-NAC-Specific Autoreactive CD8+ T Cells in Atopic Dermatitis Are of an Effector Memory Type and Secrete IL-4 and IFN-γ.
abstract: Autoreactivity may play a critical role in the chronification of atopic dermatitis (AD). Several studies showed that AD patients produce IgE Abs specific for autoantigens, and we described Th as well as CD8(+) T cells specific for the autoallergen Hom s 2, the α-chain of the nascent polypeptide-associated complex (α-NAC). This study aimed to investigate the frequency and inflammatory phenotype of autoallergen-specific CD8(+) T cells. CD8(+) T cell immunodominant epitopes of α-NAC were mapped by applying prediction softwares, and binding affinity was confirmed by stabilization of empty MHC complexes. MHC class I tetramers were assembled and binding cells were analyzed directly ex vivo by flow cytometry and in terms of single-cell assessment by ChipCytometry. We report significantly elevated numbers of α-NAC-specific peripheral T cells in sensitized patients compared with nonatopic controls. These cells secrete IL-4 and IFN-γ, and surface markers revealed significantly elevated frequencies of circulating terminally differentiated α-NAC-specific CD8(+) T cells in patients with AD compared with nonatopic donors. The observed phenotype of α-NAC-specific CD8(+) T cells indicates a role in the pathogenesis of AD.
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, 30625 Hannover, Germany; roesner.lennart@mh-hannover.de.
authors.forename: Lennart M
authors.identifier: http://orcid.org/0000-0001-6651-0458
authors.initials: LM
authors.lastname: Roesner
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Annice
authors.initials: A
authors.lastname: Heratizadeh
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Susanne
authors.initials: S
authors.lastname: Wieschowski
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
authors.forename: Irene
authors.initials: I
authors.lastname: Mittermann
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
authors.affiliation: Department of Pediatric Immunology, Allergology and Pneumology, Hannover Medical School, 30625 Hannover, Germany; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Hennig
authors.affiliation: Department of Pediatric Immunology, Allergology and Pneumology, Hannover Medical School, 30625 Hannover, Germany; and.
authors.forename: Gesine
authors.initials: G
authors.lastname: Hansen
authors.affiliation: Institute for Transplant Immunology, Integrated Research and Treatment Center Transplantation, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D018832:Molecular Chaperones / Q000276:immunology*; D011485:Protein Binding / Q000502:physiology
chemical_list: D018984:Epitopes, T-Lymphocyte; C524866:HLA-A*02 antigen; D015789:HLA-A2 Antigen; C508598:IL4 protein, human; D018832:Molecular Chaperones; C096099:nascent-polypeptide-associated complex; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma