The role of T-cell reactivity towards the autoantigen α-NAC in atopic dermatitis

Abstract

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.

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

“…In summary, we were able to describe a significantly elevated frequency of a-NAC-specific CD8 + T cells in patients with AD. Both T EMRA and T EM CD8 + T cells were strongly increased in numbers, and we detected production of the proinflammatory cytokines IL-4 and IFN-g. Because a-NAC-specific T cells express skin-homing markers and can be cloned from lesional AD skin (13), the cells identified in the present study presumably infiltrate the skin and may sustain an inflammation also in the absence of environmental allergens. Direct detection of these cells in lesional skin is planned to verify this hypothesis.…”

“…A recent meta-analysis reports autoimmune phenomena in up to 91% of AD patients, whereas in patients with allergic rhinitis, psoriasis, or systemic lupus no IgE autoreactivity could be observed (4). Recently, we reported autoreactivity on the T cell level, describing T cell clones autoreactive to the Ags a-NAC and thioredoxin (9,13). For these proteins, autoreactivity had first been described on the humoral level (7,11).…”

“…About 80% of adult AD patients bear IgE sensitization to a variety of seasonal as well as perennial aeroallergens or suffer from food allergy (13,41,42). Whereas total IgE levels are often highly elevated in AD, the specificity of IgE often remains unknown (1).…”

“…The generation of T cell clones from lesional skin and peripheral blood of patients enabled us to characterize autoallergen-specific CD8 + and CD4 + T cells (13). To extend these data and to characterize autoallergen-specific T cells in detail excluding cell culture and cloning artifacts, this study aims to identify immunodominant epitopes of a-NAC.…”

Fortschritte bei der atopischen Dermatitis

“…Auch α-NAC-Autoallergen-spezifische T-Zell-Klone, die aus läsionaler AD-Haut und dem Blut von AD-Patienten isoliert werden konnten, exprimierten IL-17 [24]. Mithilfe Filaggrin-defizienter Mäuse wurde zudem gezeigt, dass im entzündlichen Infiltrat Th17-Zellen dominierten und die epikutane Sensibilisierung gegenüber Ovalbumin begünstigt wurde [25,26].…”