title: Establishment of a vascular endothelial cell-reactive type II NKT cell clone from a rat model of autoimmune vasculitis.
abstract: We previously generated a rat model that spontaneously developed small vessel vasculitis (SVV). In this study, a T cell clone reactive with rat vascular endothelial cells (REC) was established and named VASC-1. Intravenous injection of VASC-1 induced SVV in normal recipients. VASC-1 was a TCRαβ/CD3-positive CD4/CD8 double-negative T cell clone with expression of NKG2D. The cytokine mRNA profile under unstimulated condition was positive for IL-4 and IFN-γ but negative for IL-2 and IL-10. After interaction with REC, the mRNA expression of IL-2, IL-5 and IL-6 was induced in VASC-1, which was inhibited by blocking of CD1d on the REC surface. Although the protein levels of these cytokines seemed to be lower than the detection limit in the culture medium, IFN-γ was detectable. The production of IFN-γ from the VASC-1 stimulated with LPS-pre-treated REC was inhibited by the CD1d blockade on the REC. These findings indicated VASC-1 as an NKT cell clone. The NKT cell pool includes two major subsets, namely types I and II. Type I NKT cells are characterized by expression of semi-invariant TCRs and the potential to bind to marine sponge-derived α-galactosylceramide (α-GalCer) loaded on CD1d; whereas, type II NKT cells do not manifest these characteristics. VASC-1 exhibited a usage of TCR other than the type I invariant TCR α chain and did not bind to α-GalCer-loaded CD1d; therefore, it was determined as a type II NKT cell clone. The collective evidence suggested that REC-reactive type II NKT cells could be involved in the pathogenesis of SVV in rats.
authors.affiliation: Division of Health Sciences, Graduate School of Health Sciences, Hokkaido University, Sapporo 0600812, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Iinuma
authors.affiliation: Division of Health Sciences, Graduate School of Health Sciences, Hokkaido University, Sapporo 0600812, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Waki
authors.affiliation: Division of Health Sciences, Graduate School of Health Sciences, Hokkaido University, Sapporo 0600812, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kawakami
authors.affiliation: Division of Health Sciences, Graduate School of Health Sciences, Hokkaido University, Sapporo 0600812, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 0608638, Japan.
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 0608638, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Division of Health Sciences, Graduate School of Health Sciences, Hokkaido University, Sapporo 0600812, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Division of Health Sciences, Graduate School of Health Sciences, Hokkaido University, Sapporo 0600812, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 0608638, Japan.
authors.forename: Sari
authors.initials: S
authors.lastname: Iwasaki
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 0608638, Japan Present address: Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa 9201192, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Baba
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 0608638, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 0608638, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiki
authors.affiliation: Institut für Virologie und Immunbiologie, Julius-Maximilians-Universität Würzburg, Würzburg 97078, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Paletta
authors.affiliation: Institut für Virologie und Immunbiologie, Julius-Maximilians-Universität Würzburg, Würzburg 97078, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
authors.affiliation: Division of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo 0600812, Japan aishizu@med.hokudai.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D014657:Vasculitis / Q000276:immunology* / Q000473:pathology
chemical_list: D055610:Antigens, CD1d; D016207:Cytokines; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D055655:NK Cell Lectin-Like Receptor Subfamily K; C113208:NKR-P2 protein, rat; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: small vessel vasculitis; type II NKT cell; vascular endothelial cell