title: NKT cells inhibit antigen-specific effector CD8 T cell induction to skin viral proteins.
abstract: We recently demonstrated that CD1d-restricted NKT cells resident in skin can inhibit CD8 T cell-mediated graft rejection of human papillomavirus E7-expressing skin through an IFN-γ-dependent mechanism. In this study, we examined the role of systemically derived NKT cells in regulating the rejection of skin grafts expressing viral proteins. In lymph nodes draining transplanted skin, Ag-specific CD8 T cell proliferation, cytokine production, and cytotoxic activity were impaired by NKT cells. NKT cell suppression was mediated via CD11c(+) dendritic cells. Inhibition of CD8 T cell function did not require Foxp3(+) regulatory T cells or NKT cell-secreted IFN-γ, IL-10, or IL-17. Thus, following skin grafting or immunization with human papillomavirus-E7 oncoprotein, NKT cells reduce the capacity of draining lymph node-resident APCs to cross-present Ag to CD8 T cell precursors, as evidenced by impaired expansion and differentiation to Ag-specific CD8 T effector cells. Therefore, in the context of viral Ag challenge in the skin, systemic NKT cells limit the capacity for effective priming of adaptive immunity.
authors: University of Queensland Diamantina Institute, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia.
authors: Stephen R
authors: SR
authors: Mattarollo
authors: Michelle
authors: M
authors: Yong
authors: Christina
authors: C
authors: Gosmann
authors: Allison
authors: A
authors: Choyce
authors: Dora
authors: D
authors: Chan
authors: Graham R
authors: GR
authors: Leggatt
authors: Ian H
authors: IH
authors: Frazer
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000821:virology; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000821:virology; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16