Skin enrichment of nickel-specific T cell clonotypes in allergic contact dermatitis

• Applicant: Dr. Katherina Siewert
• Subject Area: Dermatology ; Immunology ; Clinical Immunology and Allergology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 500312706

Skin contact with jewelry or other nickel-containing objects can trigger allergic contact dermatitis in sensitized individuals. Allergen-specific T cells are responsible for clinical symptoms and presumably accumulate in the skin of allergic persons. Approximately 11% of the European population is allergic to nickel as determined by epicutaneous patch testing. However, a positive patch test result does not prove that nickel is responsible for an eczema at another skin site, e.g. a piercing reaction.Alternative in vitro methods detect nickel-specific T cells via cell division or secretion of inflammatory mediators. This is not quantitative, takes several days and/or detects only a subset of nickel-specific T cells. A new approach based on the expression of the activation marker CD154 was therefore developed by our group. The CD154 assay quantifies nickel-specific naïve and memory T cells after 5 h. After stimulation of immune cells from blood with NiSO4, cellular surface markers are stained and analyzed by multiparameter flow cytometry.All blood-based in vitro methods show a similar result. Often nickel-specific T cells are equally abundant in the blood of allergic and non-allergic patients. Only in allergic patients with an acute, strong immune response is the frequency of nickel-specific T cells above background. It is currently not possible to diagnose nickel allergy reliably using blood as cellular source.Therefore, in the proposed project, allergic individuals will be identified as target tissues of an allergic reaction by enrichment of nickel-specific T cells in the skin. T cells differ in the genetic composition of their T cell receptor, so that each person has about 3x10^11 T cells with more than 10^8 receptor variants. To confirm specific enrichment, we are sequencing T cell receptors in skin and blood samples and compare them bioinformatically. In preliminary work, the hypothesis could be confirmed, as cells with nickel-specific T cell receptor were enriched in the skin only in a nickel-triggered eczema, the controls were negative.These preliminary results need to be confirmed by the analysis of additional samples for a valid conclusion. In addition, other nickel-specific T cell populations (cytotoxic and regulatory T cells, T cells with markers for skin migration) will be included in the characterization of the allergic reaction at the cellular level.As a result, we expect a detailed understanding of the infiltrating T cell populations in allergic nickel eczema, a methodology for the analysis of antigen-specific T cells in human tissues, and a definitive diagnostic tool for nickel allergy. This approach offers the only possibility so far to detect to which allergen the immune cells in the skin react and may be adapted for further allergens in the future.

• DFG Programme: Research Grants