title: Sulfatide inhibits α-galactosylceramide presentation by dendritic cells.
abstract: Sulfatide-reactive type II NKT cells, the so-called non-invariant NKT (non-iNKT) cells, have been shown to counteract invariant NKT (iNKT) cell activity. However, the effects of sulfatide on activation of iNKT cells by α-galactocylceramide (αGC) in the context of CD1d have not been studied in detail. Therefore, we studied the blocking effect of sulfatide on αGC-induced iNKT cell activation by dendritic cells (DCs). Even in the absence of non-iNKT cells, sulfatide inhibited αGC-mediated iNKT cell activation by reducing αGC/CD1d complex formations in a dose-dependent manner. This was also confirmed in a cell-free setting using immobilized CD1d-Ig. Moreover, simultaneous injection of αGC with sulfatide decreased αGC/CD1d complex formations on DCs, accompanied by the reduced CD40L-up-regulation and IFN-γ production by iNKT cells and IL-12p70 production by DCs. However, sulfatide by itself did not interfere with the presentation of MHC class II-mediated antigen presentation to specific T cells. These results demonstrate that sulfatide competes with αGC to be loaded onto CD1d along the endocytic pathway in DCs, thereby inhibiting the iNKT cell response.
authors.affiliation: Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto 606-8501, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kanamori
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tasumi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Iyoda
authors.forename: Maki
authors.initials: M
authors.lastname: Ushida
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D018949:Antigens, CD1 / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005699:Galactosylceramides / Q000378:metabolism*; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; D005699:Galactosylceramides; D013433:Sulfoglycosphingolipids; C493154:alpha-galactosylceramide; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma