Malassezia sympodialis thioredoxin-specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis

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. Conclusion 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.