Avridine-induced arthritis in rats; a T cell-dependent chronic disease influenced both by MHC genes and by non-MHC genes.
Avridine is a potent synthetic adjuvant that can induce arthritis is most rat strains. The clinical appearance and histopathology of avridine-induced arthritis show great similarity to other arthritis models such as collagen-induced arthritis. In LEW and DA rats the avridine-induced arthritis is severe and long lasting. To investigate a possible genetic influence on the disease we compared LEW, DA and E3 rats, which are of different genetic origins, for their ability to develop arthritis after injection of a low dose of avridine (1.5 mg/rat). The E3 rat was shown to be resistant, whereas all of the DA rats developed arthritis. Recombinant inbred strains derived from DA and E3 parentals varied in susceptibility to avridine. Only strains sharing RT1av1 with DA developed arthritis, indicating a role for the MHC genes. The MHC association was further analysed in a series of Lewis congenic strains using the 1.5 mg avridine dose. All strains developed arthritis. LEW.1C and LEW.1W developed only acute arthritis, whereas LEW.1A, LEW, LEW.1D, LEW.1N and LEW.1F developed chronic arthritis. In particular, the LEW.1F rats developed a chronic severe arthritis of high incidence. The chronic arthritis showed an active, erosive joint inflammation several months after induction. Nude rats are resistant to avridine-induced arthritis, indicating a T cell dependence of the disease which supports the importance of MHC. However, non-MHC genes are also crucial to arthritis development. Recombinants between DA and E3, sharing RT1av1 with DA, showed either a lower incidence or a lower severity of disease than the DA rats. The E3 rat and the recombinants with RT1u were completely resistant, whereas LEW.1W, also RT1u, were highly susceptible.
Vingsbo
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Department of Medical Inflammation Research, Lund University, Sweden.
Jonsson
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Holmdahl
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D000276:Adjuvants, Immunologic; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D003959:Diamines; D004195:Disease Models, Animal; D005260:Female; D007124:Immunoenzyme Techniques; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D003959:Diamines; C006270:avridine