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J Immunol. 2016 Apr 15;196(8):3245-52. doi: 10.4049/jimmunol.1500351. Epub 2016 Mar 9.

α-NAC-Specific Autoreactive CD8+ T Cells in Atopic Dermatitis Are of an Effector Memory Type and Secrete IL-4 and IFN-γ.

Author information

1
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, 30625 Hannover, Germany; roesner.lennart@mh-hannover.de.
2
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, 30625 Hannover, Germany;
3
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
4
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany;
5
Department of Pediatric Immunology, Allergology and Pneumology, Hannover Medical School, 30625 Hannover, Germany; and.
6
Institute for Transplant Immunology, Integrated Research and Treatment Center Transplantation, Hannover Medical School, 30625 Hannover, Germany.

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.

PMID:
26962231
DOI:
10.4049/jimmunol.1500351
[Indexed for MEDLINE]
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