title: Invariant NKT cells are expanded in peripheral blood but are undetectable in salivary glands of patients with primary Sjögren's syndrome.
abstract: OBJECTIVE
  Invariant NKT (iNKT) cells play a role in regulating the function of autoreactive B cells before their entry into germinal centres. Absence and/or reduction of iNKT cells have been demonstrated in patients with systemic lupus erythematosus (SLE) together with an increase of autoreactive B cell activity. Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease in which lymphocyte infiltration and organisation in lymphoid structures of inflamed salivary glands occurs. The aim of the study was to investigate the percentage and function of iNKT in the salivary glands and peripheral blood of patients with pSS.
  
  
  METHODS
  Minor salivary gland biopsies were obtained from patients with pSS and with non-specific chronic sialoadenitis (nSS). Flow cytometry analysis of CD1d/α-GalactosylCeramide (α-GalCer) tetramer positive cells, producing IFN-γ and IL-17, and quantitative gene expression analysis by TaqMan real-time PCR for Vα24 were performed on salivary glands biopsies and peripheral blood samples obtained from patients and controls. Flow cytometry and immunofluorescence analysis for autoreactive B lymphocytes and ELISA for anti-SSA antibodies (Ab) detection were also performed.
  
  
  RESULTS
  An increase of iNKT was detected ex vivo in peripheral blood of pSS patients; after α-GalCer stimulation this subset produce IL-17 and IFN-iNKT were undetectable in the salivary glands of pSS patients and anti-SSA specific B cells were found in target tissue. Invariant NKT cells were able to inhibit autoantibody production by B cells obtained from salivary glands of pSS.
  
  
  CONCLUSIONS
  Impaired iNKT migration to inflamed sites might induce the activation of autoreactive B cells specific for SSA-antigen in salivary glands of pSS patients.
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, and Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Raimondo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Giardina
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Alessandro
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Sireci
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Italy. giovanni.triolo@unipa.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Triolo
mesh_terms: D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D012469:Salivary Glands / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; C573415:IFNG protein, human; D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell; C035356:SS-A antibodies; C528689:Valpha24 protein, human; D007371:Interferon-gamma