Logo of clinexpimmunolLink to Publisher's site
Clin Exp Immunol. Mar 1995; 99(3): 359–363.
PMCID: PMC1534209

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Holmdahl R, Andersson M, Goldschmidt TJ, Gustafsson K, Jansson L, Mo JA. Type II collagen autoimmunity in animals and provocations leading to arthritis. Immunol Rev. 1990 Dec;118:193–232. [PubMed]
  • Holmdahl R, Vingsbo C, Hedrich H, Karlsson M, Kvick C, Goldschmidt TJ, Gustafsson K. Homologous collagen-induced arthritis in rats and mice are associated with structurally different major histocompatibility complex DQ-like molecules. Eur J Immunol. 1992 Feb;22(2):419–424. [PubMed]
  • PEARSON CM. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol Med. 1956 Jan;91(1):95–101. [PubMed]
  • Chang YH, Pearson CM, Abe C. Adjuvant polyarthritis. IV. Induction by a synthetic adjuvant: immunologic, histopathologic, and other studies. Arthritis Rheum. 1980 Jan;23(1):62–71. [PubMed]
  • Kohashi O, Aihara K, Ozawa A, Kotani S, Azuma I. New model of a synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine- induced arthritis: clinical and histologic studies in athymic nude and euthymic rats. Lab Invest. 1982 Jul;47(1):27–36. [PubMed]
  • Holmdahl R, Goldschmidt TJ, Kleinau S, Kvick C, Jonsson R. Arthritis induced in rats with adjuvant oil is a genetically restricted, alpha beta T-cell dependent autoimmune disease. Immunology. 1992 Jun;76(2):197–202. [PMC free article] [PubMed]
  • Holmdahl R, Kvick C. Vaccination and genetic experiments demonstrate that adjuvant-oil-induced arthritis and homologous type II collagen-induced arthritis in the same rat strain are different diseases. Clin Exp Immunol. 1992 Apr;88(1):96–100. [PMC free article] [PubMed]
  • Yoshino S, Kinne R, Hünig T, Emmrich F. The suppressive effect of an antibody to the alpha beta cell receptor in rat adjuvant arthritis: studies on optimal treatment protocols. Autoimmunity. 1990;7(4):255–266. [PubMed]
  • Whitehouse MW, Orr KJ, Beck FW, Pearson CM. Freund's adjuvants: relationship of arthritogenicity and adjuvanticity in rats to vehicle composition. Immunology. 1974 Aug;27(2):311–330. [PMC free article] [PubMed]
  • Battisto JR, Smith RN, Beckman K, Sternlicht M, Welles WL. Susceptibility to adjuvant arthritis in DA and F344 rats. A dominant trait controlled by an autosomal gene locus linked to the major histocompatibility complex. Arthritis Rheum. 1982 Oct;25(10):1194–1200. [PubMed]
  • Kohashi O, Pearson CM, Watanabe Y, Kotani S. Preparation of arthritogenic hydrosoluble peptidoglycans from both arthritogenic and non-arthritogenic bacterial cell walls. Infect Immun. 1977 Jun;16(3):861–866. [PMC free article] [PubMed]
  • Jonsson R, Tarkowski A, Klareskog L. A demineralization procedure for immunohistopathological use. EDTA treatment preserves lymphoid cell surface antigens. J Immunol Methods. 1986 Apr 3;88(1):109–114. [PubMed]
  • Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. [PubMed]
  • Hünig T, Wallny HJ, Hartley JK, Lawetzky A, Tiefenthaler G. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989 Jan 1;169(1):73–86. [PMC free article] [PubMed]
  • Williams AF, Galfrè G, Milstein C. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977 Nov;12(3):663–673. [PubMed]
  • Brideau RJ, Carter PB, McMaster WR, Mason DW, Williams AF. Two subsets of rat T lymphocytes defined with monoclonal antibodies. Eur J Immunol. 1980 Aug;10(8):609–615. [PubMed]
  • McMaster WR, Williams AF. Monoclonal antibodies to Ia antigens from rat thymus: cross reactions with mouse and human and use in purification of rat Ia glycoproteins. Immunol Rev. 1979;47:117–137. [PubMed]
  • Kupiec-Weglinski JW, Diamantstein T, Tilney NL, Strom TB. Therapy with monoclonal antibody to interleukin 2 receptor spares suppressor T cells and prevents or reverses acute allograft rejection in rats. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2624–2627. [PMC free article] [PubMed]
  • Robinson AP, White TM, Mason DW. Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology. 1986 Feb;57(2):239–247. [PMC free article] [PubMed]
  • Taurog JD, Sandberg GP, Mahowald ML. The cellular basis of adjuvant arthritis. II. Characterization of the cells mediating passive transfer. Cell Immunol. 1983 Aug;80(1):198–204. [PubMed]
  • Holmdahl R, Rubin K, Klareskog L, Dencker L, Gustafson G, Larsson E. Appearance of different lymphoid cells in synovial tissue and in peripheral blood during the course of collagen II-induced arthritis in rats. Scand J Immunol. 1985 Mar;21(3):197–204. [PubMed]
  • Larsson P, Holmdahl R, Dencker L, Klareskog L. In vivo treatment with W3/13 (anti-pan T) but not with OX8 (anti-suppressor/cytotoxic T) monoclonal antibodies impedes the development of adjuvant arthritis in rats. Immunology. 1985 Nov;56(3):383–391. [PMC free article] [PubMed]
  • Holmdahl R, Jonsson R, Larsson P, Klareskog L. Early appearance of activated CD4+ T lymphocytes and class II antigen-expressing cells in joints of DBA/1 mice immunized with type II collagen. Lab Invest. 1988 Jan;58(1):53–60. [PubMed]
  • Jacob CO, Hwang F. Definition of microsatellite size variants for Tnfa and Hsp70 in autoimmune and nonautoimmune mouse strains. Immunogenetics. 1992;36(3):182–188. [PubMed]
  • Powis SJ, Deverson EV, Coadwell WJ, Ciruela A, Huskisson NS, Smith H, Butcher GW, Howard JC. Effect of polymorphism of an MHC-linked transporter on the peptides assembled in a class I molecule. Nature. 1992 May 21;357(6375):211–215. [PubMed]
  • van den Berg CW, Démant P, Aerts PC, Van Dijk H. Slp is an essential component of an EDTA-resistant activation pathway of mouse complement. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10711–10715. [PMC free article] [PubMed]
  • Wordsworth P, Bell J. Polygenic susceptibility in rheumatoid arthritis. Ann Rheum Dis. 1991 Jun;50(6):343–346. [PMC free article] [PubMed]
  • Nepom GT, Erlich H. MHC class-II molecules and autoimmunity. Annu Rev Immunol. 1991;9:493–525. [PubMed]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...