Pathogenic CD8+ Epidermis-Resident Memory T Cells Displace Dendritic Epidermal T Cells in Allergic Dermatitis

• Published in: Journal of investigative dermatology Vol. 140; no. 4; pp. 806 - 815.e5
• Main Authors: Gadsbøll, Anne-Sofie Ø., Jee, Mia H., Funch, Anders B., Alhede, Maria, Mraz, Veronika, Weber, Julie F., Callender, Lauren A., Carroll, Elizabeth C., Bjarnsholt, Thomas, Woetmann, Anders, Ødum, Niels, Thomsen, Allan R., Johansen, Jeanne D., Henson, Sian M., Geisler, Carsten, Bonefeld, Charlotte M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2020
• Subjects: OOA; ACD; AhR; TRM cell; CHS; DETC
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2019.07.722

The skin is our interface with the outside world, and consequently it is exposed to a wide range of microbes and allergens. Recent studies have indicated that allergen-specific skin-resident memory T (TRM) cells play a role in allergic contact dermatitis (ACD). However, the composition and dynamics of the epidermal T-cell subsets during ACD are not known. Here we show that exposure of the skin to the experimental contact allergen DNFB results in a displacement of the normally occurring dendritic epidermal T cells (DETC) concomitant with an accumulation of epidermal CD8+CD69+CD103+ TRM cells in mice. By studying knockout mice, we provide evidence that CD8+ T cells are required for the displacement of the DETC and that DETC are not required for recruitment of CD8+ TRM cells to the epidermis following allergen exposure. We demonstrate that the magnitude of the allergic reaction correlates with the number of CD8+ epidermal TRM cells, which again correlates with allergen dose and number of allergen exposures. Finally, in an attempt to elucidate why CD8+ epidermal TRM cells persist in the epidermis, we show that CD8+ epidermal TRM cells have a higher proliferative capability and are bioenergetically more stable, displaying a higher spare respiratory capacity than DETC.