Th63 - Non-Conventional CD8+IL-13+ T Cells in Refractory Atopic Dermatitis Patients

Atopic dermatitis (AD) is a chronic skin disorder mediated by type-2 cytokines, of which IL-13 plays a central role. While the primary source of IL-13 in AD is CD4⁺ TH2 cells , non-conventional CD8⁺IL-13⁺ T-cells are an increasingly recognized source of this pathogenic cytokine. Cyclosporine A (CsA), a calcineurin inhibitor used in the treatment of AD, promotes anergy in CD4+ T-cells, but may have less efficacy on CD8+ T-cell function.  We hypothesize that CD8⁺IL-13⁺ T-cells may be differentially regulated, persist despite remission, and contributing to disease chronicity. In order to investigate CD8⁺ T-cell IL-13 production, we utilized our in vitro model, whereby PBMCs from AD patients meeting Hanifen and Rajka criteria (N=13; mean EASI 16.2; mean age 38.5 yrs) were activated for 7 days in the presence of S. aureus superantigen (SEB) +/- TSLP.  Using multiparametric flow cytometry to compare IL-13 production in CD4 and CD8 T-cell subsets, we found comparable proportions of CD8⁺IL-13⁺ T-cells expressing pSTAT6 and GATA3 in the untreated condition. Furthermore, the level of IL-13 production was similar between the two populations. In contrast, exposure to TSLP+SEB significantly expanded the number of CD4⁺ - but not CD8⁺ - IL-13⁺ T-cells, despite a significant increase in activation status (CD69) and pSTAT6 in both subsets. Using a prospective cohort of adult AD patients treated with CsA, we next aim to investigate the persistence of CD8⁺IL-13⁺ T-cells during disease remission. Our findings will allow us to gain insight on pathophysiology and potential mechanisms responsible for relapse.