A novel humanized mouse model to study antigen-specific cutaneous T cell responses in vivo

Human skin contains a significant number of T cells that support tissue homeostasis and provide protective immunity. T cell function in human skin is difficult to study due to a lack of adequate in vivo models. In this study we used immunodeficient NOD-scid IL2rγnull (NSG) mice that carried in vivo-generated engineered skin (ES) and received adoptively transferred human peripheral blood mononuclear cells. ES were generated from keratinocytes and fibroblasts only and initially contained no skin-resident immune cells. This reductionist system allowed us to study T cell recruitment and function in non-inflamed and non-infected human skin. We found that functional human T cells specifically infiltrated the human skin tissue and responded to microbial antigen in vivo. Importantly, T cell maintenance and function was supported by the microenvironment of human skin. We have thus generated a novel mouse model with broad utility in studies of human cutaneous antigen-specific T cell responses and the role of the skin microenvironment to skin immunity in vivo.