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Streptococcal Cell Wall Induced Arthritis: Leukocyte Activation in Extra-Articular Lymphoid Tissue

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Abstract

Rheumatoid arthritis (RA) is a common systemic inflammatory disease thought to be T- helper-1 cell driven, though current controversy involves the relative role of T cells versus other leukocytes. Thus, there is a need for better understanding of the role of various leukocytes and their subsets in RA. Using the streptococcal cell wall (SCW) induced arthritis model, we examined leukocytes isolated from peripheral blood, spleen, and lymph nodes using monoclonal antibodies directed against lineage specific cell surface markers. Activation status of these cells was assessed using CD44 and CD71 as markers. T cells in general, and CD4+ T cells in particular were found to be activated in spleen and lymph nodes. B cells and monocytes in spleen demonstrated increased activation as well. The activation of cells in the myeloid and lymphoid lineages in the chronic phase of arthritis indicates ongoing involvement of innate and cognate immunity. This study quantitates specific changes in B and T lymphocytes, and myeloid cells and is consistent with findings in human RA in which specific antibodies, T cells, and myeloid cells are all implicated in the pathogenesis of RA.

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References

  1. Miltenburg, A. M., J. M. van Laar, R. de Kuiper, M. R. Daha, and F. C. Breedveld. 1992. T cells cloned from human rheumatoid synovial membrane functionally represent the Th1 subset. Scand. J. Immunol. 35:603–610.

    Google Scholar 

  2. Miossec, P., and W. Van Den Berg. 1997. Th1/Th2 cytokine balance in arthritis. Arthritis Rheum. 40:2105–2115.

    Google Scholar 

  3. Quayle, A. J., P. Chomarat, P. Miossec, J. Kjeldsen-Kragh, O. Forre, and J. B. Natvig. 1993. Rheumatoid inflammatory T-cell clones express mostly Th1 but also Th2 and mixed (Th0-like) cytokine patterns. Scand. J. Immunol. 38:75–82.

    Google Scholar 

  4. Schwab, J. H. 1995. Bacterial cell-wall induced arthritis: Models of chronic recurrent polyarthritis and reactivation of monoarticular arthritis. In: Mechanisms and Models in Rheumatoid Arthritis, B. Henderson, J. C. W. Edwards, and E. R. Pettipher, eds. Academic Press, San Diego, CA, pp. 431–446.

    Google Scholar 

  5. Freemont, A. J. 1995. Histopathology of the rheumatoid joint. In: Mechanisms and Models in Rheumatoid Arthritis, B. Henderson, J. C. W. Edwards, and E. R. Pettipher, eds. Academic Press, London, pp. 83–113.

    Google Scholar 

  6. Cromartie, W. J., J. G. Craddock, J. H. Schwab, S. K. Anderle, and C. H. Yang. 1977. Arthritis in rats after systemic injection of streptococcal cells or cell walls. J. Exp. Med. 146:1585–1602.

    Google Scholar 

  7. Fuseler, J. W., M. Hearth-Holmes, M. B. Grisham, D. Kang, F. S. Laroux, and R. E. Wolf. 2000. FK506 attenuates developing and established joint inflammation and suppresses interleukin 6 and nitric oxide expression in bacterial cell wall induced polyarthritis. J. Rheumatol. 27:190–199.

    Google Scholar 

  8. Henderson, B., J. C. W. Edwards, and E. R. Pettipher. Mechanisms and Models in Rheumatoid Arthritis. Academic Press, New York.

  9. Zhang, J., B. N. Weichman, and A. J. Lewis. 1995. Role of animal models in the study of rheumatoid arthritis: An overview. In Mechanisms and Models in Rheumatoid Arthritis, B. Henderson, J. C. W. Edwards, and E. R. Pettipher, eds. Academic Press, New York, pp. 363–371.

    Google Scholar 

  10. Wahl, S. M., J. B. Allen, S. Dougherty, V. Evequoz, D. H. Pluznik, R. L. Wilder, A. R. Hand, and L. M. Wahl. 1986. T lymphocyte-dependent evolution of bacterial cell wall-induced hepatic granulomas. J. Immunol. 137:2199–2209.

    Google Scholar 

  11. Yocum, D. E., J. B. Allen, S. M. Wahl, G. B. Calandra, and R. L. Wilder. 1986. Inhibition by cyclosporin A of streptococcal cell wall-induced arthritis and hepatic granulomas in rats. Arthritis Rheum. 29:262–273.

    Google Scholar 

  12. DeJoy, S. Q., K. M. Ferguson, T. M. Sapp, J. B. Zabriskie, A. L. Oronsky, and S. S. Kerwar. 1989. Streptococcal cell wall arthritis: Passive transfer of disease with a T cell line and cross-reactivity of streptococcal cell wall antigens with Mycobacterium tuberculosis. J. Exp. Med. 170:369–382.

    Google Scholar 

  13. Yoshino, S., L. G. Cleland, G. Mayrhofer, R. R. Brown, and J. H. Schwab. 1991. Prevention of chronic erosive streptococcal cell wall-induced arthritis in rats by treatment with a monoclonal antibody against the T cell antigen receptor alpha beta. J. Immunol. 146:4187–4189.

    Google Scholar 

  14. van den Broek, M. F., L. G. Van de Langerijt, M. C. van Bruggen, M. E. Billingham, and W. B. van Den Berg. 1992. Treatment of rats with monoclonal anti-CD4 induces long-term resistance to streptococcal cell wall-induced arthritis. Eur. J. Immunol. 22:57–61.

    Google Scholar 

  15. Fuseler, J. W., E. M. Conner, J. M. Davis, R. E. Wolf, and M. B. Grisham. 1997. Cytokine and nitric oxide production in the acute phase of bacterial cell wall-induced arthritis. Inflammation 21:113–131.

    Google Scholar 

  16. Brok, H. P., J. M. Tekoppele, J. Hakimi, J. A. Kerwin, E. M. Nijenhuis, C. W. De Groot, R. E. Bontrop, and B. A. 't Hart. 2001. Prophylactic and therapeutic effects of a humanized monoclonal antibody against the IL-2 receptor (DACLIZUMAB) on collagen-induced arthritis (CIA) in rhesus monkeys. Clin. Exp. Immunol. 124:134–141.

    Google Scholar 

  17. Schimmer, R. C., D. J. Schrier, C. M. Flory, J. Dykens, D. K. Tung, P. B. Jacobson, H. P. Friedl, M. C. Conroy, B. B. Schimmer, and P. A. Ward. 1997. Streptococcal cell wall-induced arthritis. Requirements for neutrophils, P-selectin, intercellular adhesion molecule-1, and macrophage-inflammatory protein-2. J.Immunol. 159:4103–4108.

    Google Scholar 

  18. Strand, V., P. E. Lipsky, G. W. Cannon, L. H. Calabrese, C. Wiesenhutter, S. B. Cohen, N. J. Olsen, M. L. Lee, T. J. Lorenz, and B. Nelson. 1993. Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis: Results of two phase II studies. Arthritis Rheum 36(5):620–630.

    Google Scholar 

  19. Wahl, S. M., D. A. Hunt, G. Bansal, N. McCartney-Francis, L. Ellingsworth, and J. B. Allen. 1988. Bacterial cell wall-induced immunosuppression. JEM 168:1403–1417.

    Google Scholar 

  20. Wahl, S. M., J. B. Allen, K. Ohura, D. E. Chenoweth, and A. R. Hand. 1990. IFN-gamma inhibits inflammatory cell recruitment and the evolution of bacterial cell wall-induced arthritis. J. Immunol. 146:95–100.

    Google Scholar 

  21. Arend, W. P. 2001. The innate immune system in rheumatoid arthritis. Arthritis Rheum. 44:2224–2234.

    Google Scholar 

  22. McInnes, I. B. 2001. Rheumatoid arthritis. From bench to bedside. Rheum. Dis. Clin. North Am. 27:373–387.

    Google Scholar 

  23. Panayi, G. S., V. M. Corrigall, and C. Pitzalis. 2001. Pathogenesis of rheumatoid arthritis. The role of T cells and other beasts. Rheum. Dis. Clin. North Am. 27:317–334.

    Google Scholar 

  24. Smolen, J. S., and G. Steiner. 2001. Rheumatoid arthritis is more than cytokines: Autoimmunity and rheumatoid arthritis. Arthritis Rheum. 44:2218–2220.

    Google Scholar 

  25. Oppenheimer-Marks, N., and P. E. Lipsky. 1995. Leukocyte adhesion and leukocyte traffic in rheumatoid arthritis. In: Mechanisms and Models in Rheumatoid Arthritis. B. Henderson, J. C. W. Edwards, and E. R. Pettipher, eds. Academic Press, London, pp. 221–239.

    Google Scholar 

  26. Tamatani, T., M. Kotani, and M. Miyasaka. 1991. Characterization of the rat leukocyte integrin, CD11/CD18, by the use of LFA-1 subunit-specific monoclonal antibodies. Eur. J. Immunol. 21:627–633.

    Google Scholar 

  27. Liao, H. X., and B. F. Haynes. 1995. Role of adhesion molecules in the pathogenesis of rheumatoid arthritis. Rheum. Dis. Clin. North Am. 21:715–740.

    Google Scholar 

  28. Barclay, A. N., M. H. Brown, A. K. A. Law, A. J. McKnight, M. G. Tomlinson, and P. A. van der Mewe. The Leukocyte Antigen: Facts Book, 2nd edn. Academic press, Sydney, pp. 320–322.

  29. Brennan, F. R., K. Mikecz, T. T. Glant, P. Jobanputra, S. Pinder, C. Bavington, P. Morrison, and G. Nuki. 1997. CD44 expression by leucocytes in rheumatoid arthritis and modulation by specific antibody: Implications for lymphocyte adhesion to endothelial cells and synoviocytes in vitro. Scand. J. Immunol. 45: 213–220.

    Google Scholar 

  30. Brennan, F. R., J. K. O'Neill, S. J. Allen, C. Butter, G. Nuki, and D. Baker. 1999. CD44 is involved in selective leukocyte extravasation during inflammatory central nervous system disease. Immunology 98:427–435.

    Google Scholar 

  31. Haynes, B. F., L. P. Hale, K. L. Patton, M. E. Martin, and R. M. McCallum. 1991. Measurement of an adhesion molecule as an indicator of inflammatory disease activity. Up-regulation of the receptor for hyaluronate (CD44) in rheumatoid arthritis. Arthritis Rheum. 34:1434–1443.

    Google Scholar 

  32. Kelleher, D., A. Murphy, N. Hall, M. B. Omary, G. Kearns, A. Long, and E. B. Casey. 1995. Expression of CD44 on rheumatoid synovial fluid lymphocytes. Ann. Rheum. Dis. 54:566–570.

    Google Scholar 

  33. Mikecz, K., K. Dennis, M. Shi, and J. H. Kim. 1999. Modulation of hyaluronan receptor (CD44) function in vivo in a murine model of rheumatoid arthritis. Arthritis Rheum. 42:659–668.

    Google Scholar 

  34. Verdrengh, M., R. Holmdahl, and A. Tarkowski. 1995. Administration of antibodies to hyaluronan receptor (CD44) delays the start and ameliorates the severity of collagen II arthritis. Scand. J. Immunol. 42:353–358.

    Google Scholar 

  35. Firestein, G. S. 1996. Invasive fibroblast-like synoviocytes in rheumatoid arthritis. Passive responders or transformed aggressors? Arthritis Rheum. 39: 1781–1790.

    Google Scholar 

  36. Zvaifler, N. J., V. Tsai, S. Alsalameh, J. von Kempis, G. S. Firestein, and M. Lotz. 1997. Pannocytes: Distinctive cells found in rheumatoid arthritis articular cartilage erosions. Am. J. Pathol. 150:1125–1138.

    Google Scholar 

  37. Fox, D. A. 1997. The role of T cells in the immunopathogenesis of rheumatoid arthritis: New perspectives. Arthritis Rheum. 40:598–609.

    Google Scholar 

  38. Yamamura, Y., R. Gupta, Y. Morita, X. He, R. Pai, J. Endres, A. Freiberg, K. Chung, and D. A. Fox. 2001. Effector function of resting T cells: Activation of synovial fibroblasts. J. Immunol. 166:2270–2275.

    Google Scholar 

  39. Butcher, E. C., M. Williams, K. Youngman, L. Rott, and M. Briskin. 1999. Lymphocyte trafficking and regional immunity. Adv. Immunol. 72:209–253.

    Google Scholar 

  40. Miagkov, A. V., D. V. Kovalenko, C. E. Brown, J. R. Didsbury, J. P. Cogswell, S. A. Stimpson, A. S. Baldwin, and S. S. Makarov. 1998. NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc. Natl. Acad. Sci. U.S.A 95:13859–13864.

    Google Scholar 

  41. Foxwell, B., K. Browne, J. Bondeson, C. Clarke, R. de Martin, F. Brennan, and M. Feldmann. 1998. Efficient adenoviral infection with IkappaB alpha reveals that macrophage tumor necrosis factor alpha production in rheumatoid arthritis is NF-kappaB dependent. Proc. Natl. Acad. Sci. U.S.A 95:8211–8215.

    Google Scholar 

  42. Allen, J. B., D. G. Malone, S. M. Wahl, G. B. Calandra, and R. L. Wilder. 1985. Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation. J. Clin. Invest. 76:1042–1056.

    Google Scholar 

  43. Klasen, I. S., J. Kool, M. J. Melief, I. Loeve, W. B. van Den Berg, A. J. Severijnen, and M. P. Hazenberg. 1992. Arthritis by autoreactive T cell lines obtained from rats after injection of intestinal bacterial cell wall fragments. Cell. Immunol. 139:455–467.

    Google Scholar 

  44. Burmester, G. R., B. Stuhlmuller, G. Keyszer, and R. W. Kinne. 1997. Mononuclear phagocytes and rheumatoid synovitis. Mastermind or workhorse in arthritis? Arthritis Rheum. 40: 5–18.

    Google Scholar 

  45. Parnes, J. R. 1989. Molecular biology and function of CD4 and CD8. Adv. Immunol 44:265–311.

    Google Scholar 

  46. Medzhitov, R. and C. A. Janeway Jr. 1997. Innate immunity: The virtues of a nonclonal system of recognition. Cell 91:295–298.

    Google Scholar 

  47. Kobayashi, K., L. D. Hernandez, J. E. Galan, C. A. Janeway Jr., R. Medzhitov, and R. A. Flavell. 2002. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110:191–202.

    Google Scholar 

  48. Abbas, A. K., A. H. Lichtman, and J. S. Pober. 1994. Cytokines. In Cellular and Molecular Immunology. W. B., Saunders, Philadelphia, pp. 240–260.

    Google Scholar 

  49. Butler, D. M., R. N. Maini, M. Feldmann, and F. M. Brennan. 1995. Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. Comparison of monoclonal anti TNF-alpha antibody with the interleukin-1 receptor antagonist. Eur. Cytokine Network 6:225–230.

    Google Scholar 

  50. Feldmann, M., and R. N. Maini. 2001. Anti-TNF alpha therapy of rheumatoid arthritis: What have we learned? Ann. Rev. Immunol. 19: 163–196.

    Google Scholar 

  51. Maini, R. N., M. J. Elliott, F. M. Brennan, and M. Feldmann. 1995. Beneficial effects of tumour necrosis factor-alpha (TNF-alpha) blockade in rheumatoid arthritis (RA). Clin. Exp. Immunol. 101:207–212.

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Center of Excellence of Rheumatology and Arthritis, LSU Health Sciences Center, Shreveport, Louisiana

    Donald Kimpel, Tim Dayton, Krishnaswamy Kannan & Robert E. Wolf

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  1. Donald Kimpel
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  2. Tim Dayton
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Correspondence to Donald Kimpel.

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Kimpel, D., Dayton, T., Kannan, K. et al. Streptococcal Cell Wall Induced Arthritis: Leukocyte Activation in Extra-Articular Lymphoid Tissue. Inflammation 27, 59–70 (2003). https://doi.org/10.1023/A:1023215515617

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