Vδ1 T Cells Integrated in Full-Thickness Skin Equivalents: A Model for the Role of Human Skin-Resident γδT Cells

Vδ1 T cells are a subpopulation of γδT cells found in human dermis. Much less is known regarding their role and function in skin health and disease than regarding the roles of murine skin-resident γδT cells. In this study, we report the successful integration of Vδ1 T cells into long-term fibroblast-derived matrix skin equivalents. We isolated Vδ1 T cells from human blood, where they are rare, and established conditions for the integration and maintenance of the freshly isolated Vδ1 T cells in the skin equivalents. Plated on top of the dermal equivalents, almost all Vδ1 T cells migrated into the dermal matrix where they exerted their influence on both the dermal equivalents and the epithelium. Vδ1 T cells contributed to epidermal differentiation of HaCaT cells as indicated by histology, expression of epidermal differentiation markers, and RNA-sequencing expression profile. When complemented with the carcinoma-derived SCC13 cells instead of HaCaT, our data suggest a role for Vδ1 T cells in slowing growth of the tumor cells, as indicated by reduced stratification and changes in gene expression profiles. Together, we demonstrate the successful establishment of human Vδ1 T cell-competent skin equivalents and skin carcinoma equivalents and provide evidence for molecular and functional consequences of the Vδ1 T cells on their respective environment.