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The Immunogenetic Basis of Collagen Induced Arthritis in Mice: An Experimental Model for the Rational Design of Immunomodulatory Treatments of Rheumatoid Arthritis

  • Chapter
Immunobiology of Proteins and Peptides VII

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 347))

Abstract

Elucidating the genetic influences and immunological processes involved in the induction and pathogenesis of rheumatoid arthritis (RA) has been an area of intense investigation over the past two decades. During this period, various experimental animal models of RA have been studied which have contributed greatly to our basic understanding of this disease. One model of particular interest is the mouse model of collagen induced arthritis (CIA). Following the initial description of the model in rats,1 the successful induction of CIA in mice was achieved by Courtenay et al.2 CIA is usually induced by the intradermal injection of heterologous or homologous type II collagen (CII) in complete Freund’s adjuvant.3,4 Both T and B cell reactivity to CII is detected and, approximately 4–6 weeks post-immunization, mice develop a polyarthritis initially characterized by erythema and edema followed by joint distortion and, in some cases, culminating in joint ankylosis.5 Histologic examination of afflicted paws from mice with CIA reveals marked synovial proliferation, pannus formation and subsequent joint destruction with replacement by mononuclear cells.6 These clinical and histopathologic features of CIA strongly resemble those observed in human RA. Of particular importance has been the fact that the availability of numerous inbred mouse strains has enabled scientists to undertake a systematic and detailed analysis of the genetic factors contributing to this disease. Thus, understanding the immunogenetic characteristics of murine CIA strengthens the potential of this model for developing specific immune intervention strategies in human RA.

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References

  1. D.E. Trentham, A.S. Townes, and A.H. Kang, Autoimmunity to type II collagen: An experimental model of arthritis. J. Exp. Med. 146:857 (1977)

    Article  PubMed  CAS  Google Scholar 

  2. J.S. Courtenay, M.J. Dallman, A.D. Dayan, A. Martin, and B. Mosedale, Immunization against heterologous type II collagen induces arthritis in mice. Nature 285:666 (1980)

    Article  Google Scholar 

  3. S. Banerjee, B-Y. Wei, K. Hillman, H.S. Luthra, and C.S. David, Immunosuppression of collagen-induced arthritis in mice with an anti-IL-2 receptor antibody. J. Immunol. 141:1150 (1988)

    PubMed  CAS  Google Scholar 

  4. R. Holmdahl, L. Jansson, M. Andersson, and E. Larsson, Immunogenetics of type II collagen autoimmunity and susceptibility to collagen arthritis. Immunology 65:305 (1988)

    PubMed  CAS  Google Scholar 

  5. P.H. Wooley, Collagen-induced arthritis in the mouse. Meth. Enzymol. 162:361 (1988)

    Article  CAS  Google Scholar 

  6. P.H. Wooley, H.S. Luthra, J.M. Stuart, and C.S. David, Type II collagen induce arthritis mice: 1. Major histocompatibility complex (I-region) linkage and antibody correlates. J. Exp. Med. 154:688 (1981)

    Article  PubMed  CAS  Google Scholar 

  7. P. Stasny, Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N. Engl. J. Med. 298:869 (1978)

    Google Scholar 

  8. J. Tiwari, and P. Terasaki,“HLA and disease associations.” Springer-Verlag, New York, (1967)

    Google Scholar 

  9. R.W. Karr, G.E. Rodey, T. Lee, and R.D. Schwartz, Association of HLA-DRw4 with rheumatoid arthritis in black and white patients. Arthritis Rheum. 23:1241 (1980)

    Article  PubMed  CAS  Google Scholar 

  10. J.H. Dobloug, O. Forre, E. Kass, and E. Thorsby, HLA antigens and rheumatoid arthritis: association between HLA-DR4/Dw4 positivity and IgM rheumatoid factor production. Arthritis Rheum. 23:309 (1980)

    Article  PubMed  CAS  Google Scholar 

  11. P. Gregersen, M. Shen, Q. Song, P. Merryman, S. Degar, and T. Seki et al. Molecular diversity of HLA-DR4 haplotypes. Proc. Nat. Acad. Sci. 83:2642 (1986)

    Article  PubMed  CAS  Google Scholar 

  12. P.K. Gregersen, J. Silver, and R.J. Winchester, The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 30:1205 (1987)

    Article  PubMed  CAS  Google Scholar 

  13. A. Huse, P.H. Wooley, H.S. Luthra, J.M. Stuart and C.S. David, New recombinants confirm mapping of the susceptibility to type II collagen induced arthritis in mice. Fed. Proc. 43:1820 (1984)

    Google Scholar 

  14. P.H. Wooley, H.S. Luthra, M.M. Griffiths, J.M. Stuart, A. Huse, and C.S. David, Type II collagen induced arthritis in mice. IV. Variations in immunogenetic regulation provide evidence for multiple arthritogenic epitopes on the collagen molecule. J. Immunol. 135:2443 (1985)

    PubMed  CAS  Google Scholar 

  15. K. Gustafsson, M. Karlsson, L. Andersson, and R. Holmdahl, Structures on the I-A molecule predisposing for susceptibility to type II collagen-induced autoimmune arthritis. Eur. J. Immunol. 20:2127 (1990)

    Article  PubMed  CAS  Google Scholar 

  16. S. Banerjee, T.M. Haqqi, H.S. Luthra, J.M. Stuart, and C.S. David, Possible role of VßT cell receptor genes in susceptibility to collagen induced arthritis in mice. J. Exp. Med. 167:832 (1988)

    Article  PubMed  CAS  Google Scholar 

  17. H.S. Luthra, P.H. Wooley, A.M. Dillon, S.K. Singh, W.P. Lafuse, and C.J. Krco, et al. Immunogenetics of collagen-induced arthritis (CIA) in mice: a model of autoimmune disease. Ann. N.Y. Acad. Sci. 475:361 (1986)

    Article  Google Scholar 

  18. M.A. Behlke, H.S. Chow, K. Huppi, and D.Y. Loh, Murine T cell receptor mutants with deletions of ß-chain variable region genes. Proc. Nat. Acad. Sci. 83:767 (1986)

    Article  PubMed  CAS  Google Scholar 

  19. R.P. Erickson, D.K. Tachibana, L.A. Herzenberg, and L.T. Rosenberg, A single gene-controlling hemolytic complement and a serum antigen in the mouse. J. Immunol. 92:611 (1960)

    Google Scholar 

  20. W.C. Watson, and A.S. Townes, Genetic susceptibility to murine collagen II autoimmune arthritis. Proposed relationship to the IgG2 autoantibody subclass response, complement C5, major histocompatibilty complex (MHC) and non-MHC loci. J. Exp. Med. 162:1878 (1985)

    Article  PubMed  CAS  Google Scholar 

  21. S. Banerjee, G.D. Anderson, H.S. Luthra, and C.S. David, Influence of complement C5 and Vß T cell receptor mutations on susceptibility to collagen-induced arthritis in mice. J. Immunol. 142:2237 (1989)

    PubMed  CAS  Google Scholar 

  22. D.G. Spinella, J.R. Jeffers, R.A. Reife, and J.M. Stuart, The role of C5 and the T cell receptor Vß genes in susceptibility to collagen-induced arthritis. Immunogenetics 34:23 (1991)

    Article  PubMed  CAS  Google Scholar 

  23. R. Holmdahl, M. Andersson, T.J. Goldschmidt, K. Gustafsson, L. Jansson, and J.A. Mo, Type II collagen arthritis in animals and provocations leading to arthritis. Immunol. Rev. 118:193 (1990)

    Article  PubMed  CAS  Google Scholar 

  24. C. Nordling, A. Karlsson-Parra, L. Jansson, R. Holmdahl, and L. Klareskog, Characterization of a spontaneously occurring arthritis in male DBA/1 mice. Arthritis Rheum. 35:717 (1992)

    Article  PubMed  CAS  Google Scholar 

  25. T.M. Haqqi, S. Banerjee, G.A. Anderson, and C.S. David, RIIIS/J (H-2r)-an inbred mouse strain with a massive deletion of T cell receptor Vß genes. J. Exp. Med. 169:1903 (1989)

    Article  PubMed  CAS  Google Scholar 

  26. T.M. Haqqi, and C.S David, T-cell receptor Vß genes repertoire in mice possible role in resistance and susceptibility to type II collagen-induced arthritis. J. Autoimmunity 3:113 (1990)

    Article  CAS  Google Scholar 

  27. T.M. Haqqi, G.D. Anderson, S. Banerjee, and C.S. David, Restricted heterogeneity in T-cell antigen receptor Vß gene usage in the lymph nodes and arthritic joints of mice. Proc. Natl. Acad. Sci. 89:1253 (1992)

    Article  PubMed  CAS  Google Scholar 

  28. L. Mori, H. Loetscher, K. Kakimoto, H. Bluethmann, and M. Steinmetz, Expression of a transgenic T cell receptor B chain enhances collagen-induced arthritis. J. Exp. Med. 176:381 (1992)

    Article  PubMed  CAS  Google Scholar 

  29. M.D. Howell, J.P. Diveley, K.A. Lundeen, A. Esty, S.T. Winters, D.J. Carlo, and S.W. Brostoff, Limited T-cell receptor 8-chain heterogeneity among interleukin-2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis. Proc. Natl. Acad. Sci. 88:10921 (1991)

    Article  PubMed  CAS  Google Scholar 

  30. A. Sottini, L. Imberti, R. Corla, R. Cattaneo, and D. Primi, Restricted expression of T cell receptor Vß but not Vα genes in rheumatoid arthritis. Eur. J. Immunol. 21:461 (1991)

    Article  PubMed  CAS  Google Scholar 

  31. G. Pluschke, G. Ricken, H. Taube, S. Droninger, I. Melchers, and H.H. Peter, et al. Biased T cell receptor Vα region repertoire in the synovial fluid of rheumatoid arthritis patients. Eur. J. Immunol. 21:2749 (1991)

    Article  PubMed  CAS  Google Scholar 

  32. X. Paliard, S.G. West, J.A. Lafferty, J.R. Clements, J.W. Kappler, P. Marrack, and B.L. Kotzin, Evidence for the effects of a superantigen in rheumatoid arthritis. Science 253:325 (1991)

    Article  PubMed  CAS  Google Scholar 

  33. J.W. Kappler, and P. Marrack, Self-tolerance eliminates T cells specific for Mls-modified products of the Major Histocompatibility Complex. Nature 332:35 (1990)

    Article  Google Scholar 

  34. W.N. Frankel, C. Rudy, J.M. Coffin, and B.T. Huber, Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice. Nature 349:526 (1991)

    Article  PubMed  CAS  Google Scholar 

  35. G.D. Anderson, S. Banerjee, H.S. Luthra, and C.S. David, Role of the MIs-1 locus and clonal deletion of T cells in susceptibility to collagen induced arthritis in mice. J. Immunol. 147:1189 (1991)

    PubMed  CAS  Google Scholar 

  36. J.A. Todd, T.J. Aitman, R.J. Cornall, S. Ghosh, J.R.S. Hall, and C.M. Hearne, et al. Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature 351:542 (1991)

    Article  PubMed  CAS  Google Scholar 

  37. R.J. Cornall, J-B. Prins, J.A. Todd, A. Pressey, N.H. DeLarato, L.S. Wicker, and L.B. Peterson, Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1. Nature 353:262 (1991)

    Article  PubMed  CAS  Google Scholar 

  38. H-J. Garchon, P. Bedossa, L. Eloy, and J-F. Bach, Identification and mapping to chromosome 1 of a susceptibility locus for periinsulitis in non-obese diabetic mice. Nature 353:260 (1991)

    Article  PubMed  CAS  Google Scholar 

  39. R. Holmdahl, L. Klareskog, K. Rubin, J. Bjork, G. Smedegard, and R. Jonsson, Role of T lymphocytes in murine collagen induced arthritis. Agents and Actions 19:295 (1986)

    Article  PubMed  CAS  Google Scholar 

  40. J.T. Horn, L.D. Butler, P.E. Biedl, and A.M. Bendele, The progression of the inflammation in established collagen-induced arthritis can be altered by treatments with immunological or pharmacological agents which inhibit T cell activities. Eur. J. Immunol. 18:881 (1988)

    Article  Google Scholar 

  41. K.G. Moder, H.S. Luthra, R. Kubo, M. Griffiths, and C.S. David, Prevention of collagen induced arthritis in mice by treatment with an antibody directed against the T cell receptor αß framework. Autoimmunity 11:219 (1992)

    Article  PubMed  CAS  Google Scholar 

  42. K. Terato, K.A. Hasty, M.A. Cremer, J.M. Stuart, A.S. Townes, and A.H. Kang, Collagen-induced arthritis in mice. Localization of an arthritogenic determinant to a fragment of the type II collagen molecule. J. Exp. Med. 162:637 (1985)

    Article  PubMed  CAS  Google Scholar 

  43. L.K. Myers, J.M. Stuart, J. Seyer, and A.H. Kang, Identification of an immunosuppressive epitope on type II collagen that confers protection vs. collagen induced arthritis. J. Exp. Med. 170:1999 (1989)

    Article  PubMed  CAS  Google Scholar 

  44. E. Michaelsson, M. Andersson, A. Engstrom, and R. Holmdahl, Identification of an immunodominant type-II collagen peptide recognized by T cells in H-2q mice: self tolerance at the level of determinant selection. Eur. J. Immunol. 22:1819 (1992)

    Article  PubMed  CAS  Google Scholar 

  45. L.K. Myers, K. Terato, J.M. Seyer, J.M. Stuart, and A.H. Kang, Characterization of a tolerogenic T cell epitope of type II collagen and its relevance to collagen-induced arthritis. J. Immunol. 149:1439 (1992)

    PubMed  CAS  Google Scholar 

  46. P.H. Wooley, H.S. Luthra, W.P. Lafuse, A. Huse, J.M. Stuart, and C.S. David, Type II collagen-induced arthritis in mice. III. Suppression of arthritis by using monoclonal and polyclonal antiIa antisera. J. Immunol. 134:2366 (1985)

    PubMed  CAS  Google Scholar 

  47. G. Chiocchia, M.C. Boisser, and C. Fournier, Therapy against murine collagen-induced arthritis with T cell receptor Vß specific antibodies. Eur. J. Immunol. 21:2899 (1991)

    Article  PubMed  CAS  Google Scholar 

  48. G.E. Osman, M. Toda, O. Kanagawa, and L.E. Hood, Characterization of the T cell receptor repertoire causing collagen arthritis in mice. J. Exp. Med. 177:387 (1993)

    Article  PubMed  CAS  Google Scholar 

  49. A.A. Vandenbark, G. Hashim, and H. Offner, Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature 341:541 (1989)

    Article  PubMed  CAS  Google Scholar 

  50. D.C. Wraith, D.E. Smilek, D.J. Mitchell, L. Steinman, and H.O. McDevitt, Antigen recognition in autoimmune encephalomyelitis and the potential for peptide-mediated immunotherapy. Cell 59:247 (1989)

    Article  PubMed  CAS  Google Scholar 

  51. M.T. De Magistris, J. Alexander, M. Coggeshall, A. Altman, F.C.A. Gaeta, H.M. Grey, and A. Sette, Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. Cell 68:625 (1992)

    Article  PubMed  Google Scholar 

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Nabozny, G.H., David, C.S. (1994). The Immunogenetic Basis of Collagen Induced Arthritis in Mice: An Experimental Model for the Rational Design of Immunomodulatory Treatments of Rheumatoid Arthritis. In: Atassi, M.Z. (eds) Immunobiology of Proteins and Peptides VII. Advances in Experimental Medicine and Biology, vol 347. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2427-4_6

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  • DOI: https://doi.org/10.1007/978-1-4615-2427-4_6

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