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 (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 1-fluoro-2,4-dinitrobenzene (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 knock-out mice, we provide evidence that CD8+ T cells are required for the displacement of the DETC and furthermore, 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 that 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.