γδ T Cells Augment Rejection of Skin Grafts by Enhancing Cross-Priming of CD8 T Cells to Skin-Derived Antigen

Abstract

γδ T cells possess innate like properties and are proposed to bridge the gap between innate and adaptive immunity. In this study we explored the role of γδ T cells in cutaneous immunity utilizing a skin transplantation model. Following engraftment of skin expressing cell associated model antigen (ovalbumin) in epithelial keratinocytes, skin resident γδ T cells enhanced graft rejection. While effector function of CD8 T cells was intact in the absence of γδ T cells, cross priming of CD8 T cell to graft derived antigen was impaired in the absence of γδ T cells. The reduced graft rejection and graft priming of γδ T cell deficient mice was evident in both acutely inflamed and well-healed grafting models. Furthermore, expression of the CD40 activation marker on migrating dendritic cells was lower in TCRδ-/- mice compared to wildtype mice, regardless of the presence or absence of inflammation associated with grafting. These results indicate that γδ T cells enhance graft priming and consequently the likelihood of a successful immune outcome in the context of skin graft rejection suggesting that γδ T cells may be an important component of immunity to epithelial cancers or infection.