The role of T-cell reactivity towards the autoantigen α-NAC in atopic dermatitis.
BACKGROUND
A subgroup of patients with atopic dermatitis (AD) produces IgE autoantibodies to human proteins which may be present in inflamed skin and perpetuate cutaneous inflammation.


OBJECTIVE
In order to investigate mechanisms of 'autoallergy' for AD we studied T-cell responses to the autoallergen Hom s 2, the human transcriptional coactivator α-nascent polypeptide-associated complex (α-NAC).


METHODS
Specific proliferation of blood lymphocytes from 30 patients and 12 healthy control individuals was investigated by flow cytometry. The proliferation of skin- and blood-derived T cells was assessed in limiting-dilution assays. T-cell clones (TCC) were generated from peripheral blood and from biopsies of lesional skin of patients with AD and the phenotype and cytokine patterns were determined.


RESULTS
α-NAC-specific T-cell responses were detected in patients and control individuals. α-NAC induced a significantly higher proliferation of CCR4+ (compared with CCR4-) and CLA+ (compared with CLA-) T cells from the circulation. Limiting-dilution assays revealed a high proliferation of blood and skin-infiltrating lymphocytes in the presence of α-NAC compared with control cultures. α-NAC-specific TCC generated from lesional skin of AD predominantly produced interferon-γ and some TCC also produced interleukin-17. The cytokine pattern of α-NAC TCC may contribute to keratinocyte apoptosis and eczema formation in AD.


CONCLUSIONS
α-NAC-specific TCC can be generated from blood and lesional skin of patients with AD. These TCC produce not only Th2 but also Th1 cytokines which may explain the Th1 phenotype of inflammation in AD.
Heratizadeh
A
A
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, 30449 Hannover, Germany. heratizadeh.annice@mh-hannover.de
Mittermann
I
I
Balaji
H
H
Wichmann
K
K
Niebuhr
M
M
Valenta
R
R
Werfel
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
D001324:Autoantigens; D016207:Cytokines; D018832:Molecular Chaperones; C096099:nascent-polypeptide-associated complex