γ T cells augment rejection of skin grafts by enhancing cross-priming of CD8 T cells to skin-derived antigen

Abstract

Gamma delta T cells (γ 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 γ T cells in cutaneous immunity using a skin transplantation model. Following engraftment of skin expressing cell-associated model antigen (Ag) (ovalbumin) in epithelial keratinocytes, skin-resident γ T cells enhanced graft rejection. Although the effector function of CD8 T cells was intact in the absence of γ T cells, cross-priming of CD8 T cell to graft-derived Ag was impaired in the absence of γ T cells. The reduced graft rejection and graft priming of γ 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 TCR /mice compared with wild-type mice, regardless of the presence or absence of inflammation associated with grafting. These results indicate that γ T cells enhance graft priming and consequently the likelihood of a successful immune outcome in the context of skin graft rejection, suggesting that γ T cells may be an important component of immunity to epithelial cancers or infection. © 2012 The Society for Investigative Dermatology.