title: Malassezia sympodialis thioredoxin-specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis.
abstract: BACKGROUND
  IgE-mediated cross-reactivity between fungal antigens and human proteins has been described in patients with atopic dermatitis (AD), but it remains to be elucidated whether there is also cross-reactivity at the T-cell level.
  
  
  OBJECTIVE
  We sought to explore cross-reactivity at the T-cell level between the fungal thioredoxin (Mala s 13) of the skin-colonizing yeast Malassezia sympodialis and its homologous human thioredoxin (hTrx).
  
  
  METHODS
  T-cell lines (TCLs) were generated in the presence of rMala s 13 from the peripheral blood and from skin biopsy specimens of positive patch test reactions of patients with AD sensitized to Mala s 13 and hTrx. Patients with AD not sensitized to Malassezia species, healthy subjects, and patients with psoriasis served as control subjects. Mala s 13-specific T-cell clones (TCCs) were generated from TCLs. TCCs were characterized by antigen specificity, phenotype, and cytokine secretion pattern. Human keratinocytes were stimulated with IFN-γ, TNF-α, and IL-4, and the release of hTrx was determined by means of ELISA.
  
  
  RESULTS
  Mala s 13-specific TCLs and TCCs from the blood and skin of patients with AD sensitized to Mala s 13 and hTrx were fully cross-reactive with hTrx. Mala s 13- and hTrx-specific TCCs could not be generated from control subjects. The majority of cross-reactive TCCs were CD4(+) and coexpressed cutaneous lymphocyte antigen. In addition to T(H)1 and T(H)2 TCCs, we could also identify TCCs secreting IL-17 and IL-22. After stimulation with IFN-γ and TNF-α, keratinocytes released substantial amounts of thioredoxin.
  
  
  CONCLUSIONS
  In patients with AD sensitized to Malassezia species, cross-reactivity at the T-cell level to Mala s 13 and the homologous hTrx is detectable. hTrx autoreactive skin-homing T cells might be relevant for cutaneous inflammation in patients with AD.
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Hari
authors.initials: H
authors.lastname: Balaji
authors.forename: Annice
authors.initials: A
authors.lastname: Heratizadeh
authors.forename: Katja
authors.initials: K
authors.lastname: Wichmann
authors.forename: Margarete
authors.initials: M
authors.lastname: Niebuhr
authors.forename: Reto
authors.initials: R
authors.lastname: Crameri
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
mesh_terms: D000328:Adult; D000368:Aged; D000946:Antigens, Fungal / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D003429:Cross Reactions; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology; D003881:Dermatomycoses / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008290:Malassezia / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013879:Thioredoxins / Q000276:immunology*; D055815:Young Adult
chemical_list: D000946:Antigens, Fungal; D001324:Autoantigens; D013879:Thioredoxins