Invariant NKT Cells in Hyperplastic Skin Induce a Local Immune Suppressive Environment by IFN-γ Production

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-γ, 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-γ 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.