Sjögren's syndrome in mice carrying the Ipr(cg) gene and the therapeutic efficacy of an immunosuppressive agent FK506.
The influence of the Ipr(cg) gene on the development of Sjögren's syndrome was followed up to 5 months of age in male and female mice of MRL, CBA and C3H strains. In MRL-Ipr(cg) mice, focal mononuclear cell infiltration started at 2 months and became conspicuous after 3 months of age in the lacrimal and submandibular glands but was minimal in the parotid and sublingual glands, even at 5 months of age, without any apparent sex effects found. In CBA and C3H mice carrying the Ipr(cg) gene, this manifestation of Sjögren's syndrome was much less prominent, indicating that the participation of some genes of the MRL strain may be indispensable for the development of Sjögren's syndrome in mice carrying this gene. In MRL-Ipr(cg) mice, an immunosuppressive agent, FK506, improved the serological abnormalities (decreased levels of anti-double-stranded DNA antibody of IgG2a and IgG3 subclasses) and proteinuria. It also reduced the manifestations of Sjögren's syndrome when it was intraperitoneally administered three times weekly at a dose of 2 mg/kg from 6 weeks (before disease onset) until 5 months of age (the termination of the experiment). Although VP8.2+ T cells have been demonstrated to be responsible for causing several autoimmune diseases, the selective deletion of Vp8.2+ T cells with the superantigen encoded by mouse mammary tumor virus did not affect the disease severity at all, suggesting that this T cell repertoire may not play a crucial role in induction of Sjögren's syndrome.
Yang
J
J
Department of Patholgy, Kansai Medical University, Moriguchi, Osaka, Japan.
Shikata
N
N
Yasuda
T
T
Matsuzawa
A
A
Tsubura
A
A
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D004247:DNA / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000032:analysis; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D019463:Mice, Inbred MRL lpr; D011507:Proteinuria / Q000188:drug therapy; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013363:Submandibular Gland / Q000187:drug effects / Q000473:pathology; D016559:Tacrolimus / Q000627:therapeutic use*; D019014:fas Receptor / Q000235:genetics*
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D019014:fas Receptor; D004247:DNA; D016559:Tacrolimus