title: Location of immunization and interferon-γ are central to induction of salivary gland dysfunction in Ro60 peptide immunized model of Sjögren's syndrome.
abstract: BACKGROUND
  Anti-Ro antibodies can be found in the serum of the majority of patients with Sjögren's syndrome (SS). Immunization with a 60-kDa Ro peptide has been shown to induce SS-like symptoms in mice. The aim of this study was to investigate factors involved in salivary gland (SG) dysfunction after immunization and to test whether the induction of SS could be improved.
  
  
  METHODS
  Ro60 peptide immunization was tested in Balb/c mice, multiple antigenic peptide (MAP)-Ro60 and Pertussis toxin (PTX) were tested in SJL/J mice. In addition, two injection sites were compared in these two strains: the abdominal area and the tailbase. Each group of mice was tested for a loss of SG function, SG lymphocytic infiltration, anti-Ro and anti-La antibody formation, and cytokine production in cultured cells or homogenized SG extracts.
  
  
  RESULTS
  Ro60 peptide immunization in the abdominal area of female Balb/c mice led to impaired SG function, which corresponded with increased Th1 cytokines (IFN-γ and IL-12) systemically and locally in the SG. Moreover, changing the immunization conditions to MAP-Ro60 in the abdominal area, and to lesser extend in the tailbase, also led to impaired SG function in SJL/J mice. As was seen in the Balb/c mice, increased IFN-γ in the SG draining lymph nodes accompanied the SG dysfunction. However, no correlation was observed with anti-MAP-Ro60 antibody titers, and there was no additional effect on disease onset or severity.
  
  
  CONCLUSIONS
  Effective induction of salivary gland dysfunction after Ro60 peptide immunization depended on the site of injection. Disease induction was not affected by changing the immunization conditions. However, of interest is that the mechanism of action of Ro60 peptide immunization appears to involve an increase in Th1 cytokines, resulting in the induction of SG dysfunction.
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Hongen
authors.initials: H
authors.lastname: Yin
authors.forename: Jelle L
authors.initials: JL
authors.lastname: Vosters
authors.forename: Nienke
authors.initials: N
authors.lastname: Roescher
authors.forename: Anil
authors.initials: A
authors.lastname: D'Souza
authors.forename: Biji T
authors.initials: BT
authors.lastname: Kurien
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: John A
authors.initials: JA
authors.lastname: Chiorini
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007267:Injections; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012261:Ribonucleoproteins / Q000276:immunology*; D012469:Salivary Glands / Q000276:immunology* / Q000503:physiopathology*; D012472:Salivation; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000503:physiopathology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D000099207:SS-A Antigen
chemical_list: D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D007371:Interferon-gamma; D012261:Ribonucleoproteins; D000099207:SS-A Antigen