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. 1986 Nov;66(2):320–330.

Monoclonal anti-Ia antibodies suppress the flare up reaction of antigen induced arthritis in mice.

M F van den Broek, W B van den Berg, L B van de Putte
PMCID: PMC1542525  PMID: 2949898

Abstract

Intravenous injection of methylated bovine serum albumin (mBSA) in mice with a unilateral antigen-induced arthritis induced with mBSA causes a flare up of the inflammation in the arthritic but not in the contralateral joint. To study whether this phenomenon is dependent on class II antigens, we treated C57Bl/10 (H-2b) and C3H (H-2k) mice with monoclonal anti-Iab (HB26) and anti-Iak (2-2-1) antibodies on days -3, -2, -1 and 0 before induction of the flare up. Another group was treated only once on day 0 before antigen challenge. Four injections with HB26 completely suppressed the flare up reaction in C57Bl/10 mice; the same results were seen with 2-2-1 in C3H mice. One injection only partly suppressed the flare up reaction in both strains, whereas four injections with the haplotype-nonspecific antibodies did not affect the flare up. Injections with HB26 appeared to be able to completely suppress a delayed type hypersensitivity reaction but not a reversed passive Arthus reaction in C57B1/10 mice, indicating that anti-Ia antibodies have an effect on lymphocyte-dependent but not on antigen-antibody-dependent inflammatory phenomena. These results demonstrate that the flare up of antigen induced arthritis is dependent on the presence of Ia antigens, suggesting that the interaction between antigen-presenting cells and T lymphocytes plays an important role in this process.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbas A. K., Haber S., Rock K. L. Antigen presentation by hapten-specific B lymphocytes. II. Specificity and properties of antigen-presenting B lymphocytes, and function of immunoglobulin receptors. J Immunol. 1985 Sep;135(3):1661–1667. [PubMed] [Google Scholar]
  2. Adelman N. E., Watling D. L., McDevitt H. O. Treatment of (NZB x NZW)F1 disease with anti-I-A monoclonal antibodies. J Exp Med. 1983 Oct 1;158(4):1350–1355. doi: 10.1084/jem.158.4.1350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berden J. H., Hang L., McConahey P. J., Dixon F. J. Analysis of vascular lesions in murine SLE. I. Association with serologic abnormalities. J Immunol. 1983 Apr;130(4):1699–1705. [PubMed] [Google Scholar]
  4. Cowing C., Pincus S. H., Sachs D. H., Dickler H. B. A subpopulation of adherent accessory cells bearing both I-A and I-E or C subregion antigens is required for antigen-specific murine T lymphocyte proliferation. J Immunol. 1978 Nov;121(5):1680–1686. [PubMed] [Google Scholar]
  5. Hodes R. J., Hathcock K. S., Singer A. Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-Ak reagent blocks helper T cell recognition of self major histocompatibility complex determinants. J Exp Med. 1980 Dec 1;152(6):1779–1794. doi: 10.1084/jem.152.6.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Janossy G., Panayi G., Duke O., Bofill M., Poulter L. W., Goldstein G. Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation. Lancet. 1981 Oct 17;2(8251):839–842. doi: 10.1016/s0140-6736(81)91107-7. [DOI] [PubMed] [Google Scholar]
  7. Jansen L. H., Bleumink E. Flare and rash reactions in contact allergy of the guinea-pig. Br J Dermatol. 1970;83(Suppl):48–55. [PubMed] [Google Scholar]
  8. Klareskog L., Forsum U., Scheynius A., Kabelitz D., Wigzell H. Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3632–3636. doi: 10.1073/pnas.79.11.3632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kruisbeek A. M., Titus J. A., Stephany D. A., Gause B. L., Longo D. L. In vivo treatment with monoclonal anti-I-A antibodies: disappearance of splenic antigen-presenting cell function concomitant with modulation of splenic cell surface I-A and I-E antigens. J Immunol. 1985 Jun;134(6):3605–3614. [PubMed] [Google Scholar]
  10. Lamb J. R., Eckels D. D., Ketterer E. A., Sell T. W., Woody J. N. Antigen-specific human T lymphocyte clones: mechanisms of inhibition of proliferative responses by xenoantiserum to human nonpolymorphic HLA-DR antigens. J Immunol. 1982 Sep;129(3):1085–1090. [PubMed] [Google Scholar]
  11. Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
  12. Lems S. P., Tax W. J., Capel P. J., Koene R. A. Immune regulation by monoclonal antibodies: failure to enhance mouse skin allografts. J Immunol. 1983 Jul;131(1):86–91. [PubMed] [Google Scholar]
  13. Lens J. W., van den Berg W. B., van de Putte L. B. Flare-up of antigen-induced arthritis in mice after challenge with intravenous antigen: studies on the characteristics of and mechanisms involved in the reaction. Clin Exp Immunol. 1984 Feb;55(2):287–294. [PMC free article] [PubMed] [Google Scholar]
  14. Lens J. W., van den Berg W. B., van de Putte L. B. Quantitation of arthritis by 99mTc-uptake measurements in the mouse knee-joint: correlation with histological joint inflammation scores. Agents Actions. 1984 Jun;14(5-6):723–728. doi: 10.1007/BF01978915. [DOI] [PubMed] [Google Scholar]
  15. Lens J. W., van den Berg W. B., van de Putte L. B., Zwarts W. A. Flare of antigen-induced arthritis in mice after intravenous challenge. Kinetics of antigen in the circulation and localization of antigen in the arthritic and noninflamed joint. Arthritis Rheum. 1986 May;29(5):665–674. doi: 10.1002/art.1780290512. [DOI] [PubMed] [Google Scholar]
  16. Longo D. L., Schwartz R. H. Inhibition of antigen-induced proliferation of T cells from radiation-induced bone marrow chimeras by a monoclonal antibody directed against an Ia determinant on the antigen-presenting cell. Proc Natl Acad Sci U S A. 1981 Jan;78(1):514–518. doi: 10.1073/pnas.78.1.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Muchmore A. V., Megson M., Decker J. M., Knudsen P., Mann D. L., Broder S. Inhibitory activity of antibodies to human Ia-like determinants: comparison of intact and pepsin-digested antibodies. J Immunol. 1983 Aug;131(2):725–730. [PubMed] [Google Scholar]
  18. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  19. Perry L. L., Greene M. I. Conversion of immunity to suppression by in vivo administration of I-A subregion-specific antibodies. J Exp Med. 1982 Aug 1;156(2):480–491. doi: 10.1084/jem.156.2.480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pincus S. H., Clegg D. O., Ward J. R. Characterization of T cells bearing HLA-DR antigens in rheumatoid arthritis. Arthritis Rheum. 1985 Jan;28(1):8–15. doi: 10.1002/art.1780280103. [DOI] [PubMed] [Google Scholar]
  21. Prud'homme G. J., Sohn U., Delovitch T. L. The role of H-2 and Ia antigens in graft-versus-host reactions (GVHR). Presence of host alloantigens on donor cells after GVHR and suppression of GVHR with an anti-Ia antiserum against hose Ia antigens. J Exp Med. 1979 Jan 1;149(1):137–149. doi: 10.1084/jem.149.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rosenbaum J. T., Adelman N. E., McDevitt H. O. In vivo effects of antibodies to immune response gene products. I. Haplotype-specific suppression of humoral immune responses with a monoclonal anti-I-A. J Exp Med. 1981 Nov 1;154(5):1694–1702. doi: 10.1084/jem.154.5.1694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sany J., Clot J., Bonneau M., Andary M. Immunomodulating effect of human placenta-eluted gamma globulins in rheumatoid arthritis. Arthritis Rheum. 1982 Jan;25(1):17–24. doi: 10.1002/art.1780250103. [DOI] [PubMed] [Google Scholar]
  24. Scheper R. J., von Blomberg M., Boerrigter G. H., Bruynzeel D., van Dinther A., Vos A. Induction of immunological memory in the skin. Role of local T cell retention. Clin Exp Immunol. 1983 Jan;51(1):141–148. [PMC free article] [PubMed] [Google Scholar]
  25. Schwartz R. H., Yano A., Paul W. E. Interaction between antigen-presenting cells and primed T lymphocytes: an assessment of Ir gene expression in the antigen-presenting cell. Immunol Rev. 1978;40:153–180. doi: 10.1111/j.1600-065x.1978.tb00405.x. [DOI] [PubMed] [Google Scholar]
  26. Sprent J. Effects of blocking helper T cell induction in vivo with anti-Ia antibodies. Possible role of I-A/E hybrid molecules as restriction elements. J Exp Med. 1980 Oct 1;152(4):996–1010. doi: 10.1084/jem.152.4.996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sriram S., Steinman L. Anti I-A antibody suppresses active encephalomyelitis: treatment model for diseases linked to IR genes. J Exp Med. 1983 Oct 1;158(4):1362–1367. doi: 10.1084/jem.158.4.1362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sunshine G. H., Gold D. P., Wortis H. H., Marrack P., Kappler J. W. Mouse spleen dendritic cells present soluble antigens to antigen-specific T cell hybridomas. J Exp Med. 1983 Nov 1;158(5):1745–1750. doi: 10.1084/jem.158.5.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Waldor M. K., Hardy R. R., Hayakawa K., Steinman L., Herzenberg L. A., Herzenberg L. A. Disappearance and reappearance of B cells after in vivo treatment with monoclonal anti-I-A antibodies. Proc Natl Acad Sci U S A. 1984 May;81(9):2855–2858. doi: 10.1073/pnas.81.9.2855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Waldor M. K., Sriram S., McDevitt H. O., Steinman L. In vivo therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor. Proc Natl Acad Sci U S A. 1983 May;80(9):2713–2717. doi: 10.1073/pnas.80.9.2713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wooley P. H., Luthra H. S., Lafuse W. P., Huse A., Stuart J. M., David C. S. Type II collagen-induced arthritis in mice. III. Suppression of arthritis by using monoclonal and polyclonal anti-Ia antisera. J Immunol. 1985 Apr;134(4):2366–2374. [PubMed] [Google Scholar]
  32. van de Putte L. B., Lens J. W., van den Berg W. B., Kruijsen M. W. Exacerbation of antigen-induced arthritis after challenge with intravenous antigen. Immunology. 1983 May;49(1):161–167. [PMC free article] [PubMed] [Google Scholar]
  33. van den Berg W. B., van Beusekom H. J., van de Putte L. B., Zwarts W. A., van der Sluis M. Antigen handling in antigen-induced arthritis in mice: an autoradiographic and immunofluorescence study using whole joint sections. Am J Pathol. 1982 Jul;108(1):9–16. [PMC free article] [PubMed] [Google Scholar]
  34. van den Berg W. B., van de Putte L. B., Zwarts W. A., Joosten L. A. Electrical charge of the antigen determines intraarticular antigen handling and chronicity of arthritis in mice. J Clin Invest. 1984 Nov;74(5):1850–1859. doi: 10.1172/JCI111604. [DOI] [PMC free article] [PubMed] [Google Scholar]

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