CD8+ Skin-Resident Memory T Cells Require TCR Signaling for their Persistence in a Mouse Model of Allergic Contact Dermatitis

Abstract

CD8⁺ epidermal-resident memory T (T_RM) cells play a significant role in fighting off pathogens. However, CD8⁺ T_RM cells are also central in the pathogenesis of a variety of inflammatory skin diseases. It is unclear whether the generation and persistence of CD8⁺ T_RM cells are dependent on the presence of cognate antigen and TCR signaling. The purpose of this study was to determine whether TCR signaling is required for the generation and persistence of epidermal CD8⁺ T_RM cells in a mouse model for allergic contact dermatitis. We examined the responses to 4 different contact allergens in combination with adoptive transfer and prime-pull experiments. We determined the presence of contact allergen in the skin by western blot analysis. We found that epidermal CD8⁺ T_RM cells can develop in the absence of the cognate antigen and TCR signaling as determined by Nur77 induction, whereas persistence of epidermal CD8⁺ T_RM cells requires the presence of the cognate antigen and correlates with Nur77 expression. In the presence of contact allergen, a selective expansion of specific TCR clonotypes was seen. In conclusion, this study supports that cognate antigen and TCR signaling are required for the persistence of allergen-specific CD8⁺ T_RM cells in the skin.

Keywords: Allergic contact dermatitis; Epidermis; Nur77; TCR; Tissue-resident memory T cells.