Invariant NKT cells in hyperplastic skin induce a local immune suppressive environment by IFN-gamma production.
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.
Mattarollo
Stephen R
SR
The University of Queensland Diamantina Institute, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
Rahimpour
Azad
A
Choyce
Allison
A
Godfrey
Dale I
DI
Leggatt
Graham R
GR
Frazer
Ian H
IH
D000818:Animals; D055610:Antigens, CD1d / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology; D006801:Humans; D006965:Hyperplasia; D007108:Immune Tolerance / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D046509:Tissue Culture Techniques
D055610:Antigens, CD1d; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma