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

Abstract

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 (T_RM) 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⁺ T_RM 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⁺ T_RM cells to the epidermis following allergen exposure. We demonstrate that the magnitude of the allergic reaction correlates with the number of CD8⁺ epidermal T_RM cells, which again correlates with allergen dose and number of allergen exposures. Finally, in an attempt to elucidate why CD8⁺ epidermal T_RM cells persist in the epidermis, we show that CD8⁺ epidermal T_RM cells have a higher proliferative capability and are bioenergetically more stable, displaying a higher spare respiratory capacity than DETC.