[show abstract][hide abstract] ABSTRACT: Gamma delta T cells (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 using a skin transplantation model. Following engraftment of skin expressing cell-associated model antigen (Ag) (ovalbumin) in epithelial keratinocytes, skin-resident γδ T cells enhanced graft rejection. Although the effector function of CD8 T cells was intact in the absence of γδ T cells, cross-priming of CD8 T cell to graft-derived Ag 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 with wild-type 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.
Journal of Investigative Dermatology 02/2012; 132(6):1656-64. · 6.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: NKT cells can promote or inhibit adaptive immune responses. Cutaneous immunity is tightly regulated by cooperation between innate and adaptive immune processes, but the role of NKT cells in regulating cutaneous immunity is largely unknown. In this study, we show, in a mouse model, that skin-infiltrating CD1d-restricted NKT cells in HPV16-E7 transgenic hyperplastic skin produce IFN-gamma, which can prevent rejection of HPV16-E7-expressing skin grafts. Suppression of graft rejection is associated with the accumulation of CD1d(hi)-expressing CD11c(+)F4/80(hi) myeloid cells in hyperplastic skin. Blockade of CD1d, removal of NKT cells, or local inhibition of IFN-gamma signaling is sufficient to restore immune-mediated graft rejection. Thus, inhibition of NKT cell recruitment or function may enable effective immunity against tumor and viral Ags expressed in epithelial cells.
The Journal of Immunology 12/2009; 184(3):1242-50. · 5.52 Impact Factor