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

Epidermal-resident memory CD8⁺ 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 T cell receptor (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 four 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 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.