Rheumatic diseases in an MRL strain of mice with a deficit in the functional Fas ligand

Mituko R. Ito, Shizuko Terasaki, Junpei Itoh, Hideki Katoh, Shin Yonehara, Masato Nose

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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. Conclusion. 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.

Original languageEnglish
Pages (from-to)1054-1063
Number of pages10
JournalArthritis and Rheumatism
Volume40
Issue number6
DOIs
Publication statusPublished - 1997 Jun 20

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Ito, M. R., Terasaki, S., Itoh, J., Katoh, H., Yonehara, S., & Nose, M. (1997). Rheumatic diseases in an MRL strain of mice with a deficit in the functional Fas ligand. Arthritis and Rheumatism, 40(6), 1054-1063. https://doi.org/10.1002/art.1780400610