title: Rheumatic diseases in an MRL strain of mice with a deficit in the functional Fas ligand.
abstract: OBJECTIVE
  To characterize Fas antigen expression on the cell surface, and to determine the effect of this expression in rheumatic diseases using a newly established gld-congenic MRL strain of mice (MRL/gld), which is defective in its functional Fas ligand (Fas-L).
  
  
  METHODS
  Flow cytometric analyses of lymphoid cells and macrophages were performed using anti-Fas and other cell surface markers. Histopathologic manifestations were examined using immunochemistry and light and electron microscopy. Serum levels of IgG and anti-DNA antibodies were measured by single radial immunodiffusion and enzyme-linked immunosorbent assay, respectively.
  
  
  RESULTS
  MRL/gld mice developed systemic lymphadenopathy with an accumulation of Thy1.2+, B220+ and CD4-, CD8- T cells, which both express the Fas antigen. Splenic B cells positive for surface IgM and/or surface IgD, and resident peritoneal macrophages exhibited up-regulated expression of the Fas antigen, at much higher levels than those observed in MRL/MpJ-+/+ (MRL/+) mice. Forms of rheumatic disease were observed in these mice, although not in C3H/HeJ-gld/gld mice. These forms included diffuse glomerulonephritis, granulomatous arteritis, and arthritis, and were associated with the infiltration of mononuclear cells expressing the Fas antigen. Serum levels of IgG and anti-DNA antibodies were significantly increased in MRL/gld mice compared with MRL/+ mice.
  
  
  CONCLUSIONS
  Rheumatic disease was generated by the gld gene in mice with an MRL background, as it is by the lpr gene, which is a Fas deletion mutant, associated with autoimmune traits. Rheumatic disease in this MRL strain was initiated by an incapacity for Fas/Fas-L-induced apoptosis, resulting in the development of autoimmunity and allowing for a persistent immune response in the affected lesions.
authors.affiliation: Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M R
authors.initials: MR
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Terasaki
authors.forename: J
authors.initials: J
authors.lastname: Itoh
authors.forename: H
authors.initials: H
authors.lastname: Katoh
authors.forename: S
authors.initials: S
authors.lastname: Yonehara
authors.forename: M
authors.initials: M
authors.lastname: Nose
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000974:Antibodies, Antinuclear / Q000097:blood; D017209:Apoptosis / Q000276:immunology; D001168:Arthritis / Q000209:etiology; D016516:CD4-CD8 Ratio; D029742:Caenorhabditis elegans Proteins; D004277:DNA, Single-Stranded; D053222:Fas Ligand Protein; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology; D015801:Helminth Proteins / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D008221:Lymphoid Tissue / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr / Q000235:genetics* / Q000502:physiology*; D012216:Rheumatic Diseases / Q000473:pathology* / Q000503:physiopathology*; D015854:Up-Regulation; D014657:Vasculitis / Q000209:etiology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
chemical_list: D000906:Antibodies; D000974:Antibodies, Antinuclear; D029742:Caenorhabditis elegans Proteins; D004277:DNA, Single-Stranded; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C094448:GLD-1 protein, C elegans; D015801:Helminth Proteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D019014:fas Receptor