Chapter 10 : Pathogenetic Mechanisms and Therapeutic Approaches in Superantigen-Induced Experimental Autoimmune Diseases

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Pathogenetic Mechanisms and Therapeutic Approaches in Superantigen-Induced Experimental Autoimmune Diseases, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815844/9781555814243_Chap10-1.gif /docserver/preview/fulltext/10.1128/9781555815844/9781555814243_Chap10-2.gif


In principle, three distinct mechanisms mediate superantigenic impact on the onset/relapse of autoimmune disease. First, superantigens may, following presentation on antigen-presenting cells, directly activate autoreactive T and B cells, which will migrate to the appropriate organ and once there contribute to tissue destruction by production of chemokines, proinflammatory cytokines, and tissue destructive proteinases. Second, innocent (i.e., nonautoreactive) bystander lymphocytes will be activated, thereby triggering nonspecific inflammatory response that might lead to disease relapse in the chronic phase of autoimmune disease. Finally, superantigens are able to activate the antigen-presenting cells, such as macrophages. Microbial superantigens encompass viral and bacterial proteins that share the ability to interact with major histocompatibility complex (MHC) class II and the T-cell receptor, thereby bypassing the conventional antigen-processing pathway. Superantigens have been implicated in several inflammatory diseases with and without autoimmune background. With these conditions one can include Kawasaki syndrome, psoriasis, rheumatoid arthritis, autoimmune myositis, and diabetes mellitus. Superantigens are able to interact with synoviocytes thereby triggering their production of chemokines (RANTES, monocyte chemoattractant protein-1 [MCP-1], and interleukin-8 [IL-8]). It has been clear for a decade that microbial superantigens have a significant impact on the expression of autoimmune and immune-mediated diseases. Indeed, depending on the timing and dose of superantigen, injecting of superantigen may affect the incidence and course of an autoimmune disease. Further studies on the therapeutic uses of superantigens as well as specific silencing of superantigen-mediated aberrant immune responses are definitely merited.

Citation: Tarkowski A. 2007. Pathogenetic Mechanisms and Therapeutic Approaches in Superantigen-Induced Experimental Autoimmune Diseases, p 159-168. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch10
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Abdelnour, A.,, T. Bremell,, R. Holmdahl, and, A. Tarkowski. 1994. Clonal expansion of T lymphocytes causes arthritis and mortality in mice infected with toxic shock syndrome toxin-1-producing staphylococci. Eur. J. Immunol. 24: 11611166.
2. Abdelnour, A.,, T. Bremell, and, A. Tarkowski. 1994. Toxic shock syndrome toxin 1 contributes to the arthritogenicity of Staphylococcus aureus. J. Infect. Dis. 170: 9499.
3. Abdelnour, A., and, A. Tarkowski. 1993. Polyclonal B–cell activation by an arthritogenic Staphylococcus aureus strain: contribution of T–cells and monokines. Cell. Immunol. 147: 279293.
4. Andersen, P. S.,, P. M. Lavoie,, R. P. Sekaly,, H. Churchill,, D. M. Kranz,, P. M. Schlievert,, K. Karjalainen, and, R. A. Mariuzza. 1999. Role of the T cell receptor alpha chain in stabilizing TCR–superantigen–MHC class II complexes. Immunity 10: 473483.
5. Annane, D.,, V. Sebille,, C. Charpentier,, P. E. Bollaert,, B. Francois,, J. M. Korach,, G. Capellier,, Y. Cohen,, E. Azoulay,, G. Troche,, P. Chaumet–Riffaut, and, E. Bellissant. 2002. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288: 862871.
6. Arad, G.,, D. Hillman,, R. Levy, and, R. Kaempfer. 2001. Superantigen antagonist blocks Th1 cytokine gene induction and lethal shock. J. Leukoc. Biol. 69: 921927.
7. Arad, G.,, R. Levy,, D. Hillman, and, R. Kaempfer. 2000. Superantigen antagonist protects against lethal shock and defines a new domain for T–cell activation. Nat. Med. 6: 414421.
8. Balaban, N.,, L. V. Collins,, J. S. Cullor,, E. B. Hume,, E. Medina–Acosta,, O. Vieira da Motta,, R. O’Callaghan,, P. V. Rossitto,, M. E. Shirtliff,, L. Serafim da Silveira,, A. Tarkowski, and, J. V. Torres. 2001. Prevention of diseases caused by Staphylococcus aureus using the peptide RIP. Peptides 21: 13011311.
9. Bavari, S.,, B. Dyas, and, R. G. Ulrich. 1996. Superantigen vaccines: a comparative study of genetically attenuated receptor–binding mutants of staphylococcal enterotoxin A. J. Infect. Dis. 174: 338345.
10. Bean, A. G.,, R. A. Freiberg,, S. Andrade,, S. Menon, and, A. Zlotnik. 1993. Interleukin 10 protects mice against staphylococcal enterotoxin B–induced lethal shock. Infect. Immun. 61: 49374939.
11. Bernard, G. R.,, J. L. Vincent,, P. F. Laterre,, S. P. LaRosa,, J. F. Dhainaut,, A. Lopez–Rodriguez,, J. S. Steingrub,, G. E. Garber,, J. D. Helterbrand,, E. W. Ely, and, C. J. Fisher, Jr. 2001. Efficacy and safety of recombinant human activated protein C for severe sepsis. N. Engl. J. Med. 344: 699709.
12. Boehncke, W. H.,, T. M. Zollner,, D. Dressel, and, R. Kaufmann. 1997. Induction of psoriasiform inflammation by a bacterial superantigen in the SCID–hu xenogeneic transplantation model. J. Cutan. Pathol. 24: 17.
13. Bremell, T.,, A. Abdelnour, and, A. Tarkowski. 1992. Histopathological and serological progression of experimental Staphylococcus aureus arthritis. Infect. Immun. 60: 29762985.
14. Brocke, S.,, A. Gaur,, C. Piercy,, A. Gautam,, K. Gijbels,, C. G. Fathman, and, L. Steinman. 1993. Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen. Nature 365: 642644.
15. Cole, B. C., and, M. M. Griffiths. 1993. Triggering and exacerbation of autoimmune arthritis by the Mycoplasma arthritidis superantigen MAM. Arthritis Rheum. 36: 9941002.
16. Collins, L. V.,, K. Eriksson,, R. G. Ulrich, and, A. Tarkowski. 2002. Mucosal tolerance to a bacterial super–antigen indicates a novel pathway to prevent toxic shock. Infect. Immun. 70: 22822287.
17. Collins, L. V.,, S. Hajizadeh,, E. Holme,, I. M. Jonsson, and, A. Tarkowski. 2004. Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses. J. Leukoc. Biol. 75: 9951000.
18. Hotchkiss, R. S.,, P. E. Swanson,, C. M. Knudson,, K. C. Chang,, J. P. Cobb,, D. F. Osborne,, K. M. Zollner,, T. G. Buchman,, S. J. Korsmeyer, and, I. E. Karl. 1999. Overexpression of Bcl–2 in transgenic mice decreases apoptosis and improves survival in sepsis. J. Immunol. 162: 41484156.
19. Kageyama, Y.,, Y. Koide,, T. Nagata,, M. Uchijama,, A. Yoshida,, T. Arai,, T. Miura,, C. Miyamoto, and, A. Nagano. 2001. Toxic shock syndrome toxin–1 accelerated collagen–induced arthritis in mice. J. Autoimmun. 16:125–131.
20. Kim, C.,, K. A. Siminovitch, and, A. Ochi. 1991. Reduction of lupus nephritis in MRL/lpr mice by a bacterial superantigen treatment. J. Exp. Med. 174: 14311437.
21. Kokkola, R.,, E. Sundberg,, A. C. Avebrger,, K. Palmblad,, H. Yang,, K. J. Tracey,, U. Andersson, and, H. E. Harris. 2003. Successful treatment of collagen–induced arthritis in mice and rats by targeting extracellular high mobility group box chromosomal protein 1 activity. Arthritis Rheum. 48: 20522058.
22. Lehnert, N. M.,, D. L. Allen,, P. Catasti,, P. R. Shiflett,, M. Chen,, B. E. Lehnert, and, G. Gupta. 2001. Structure–based design of a bispecific receptor mimic that inhibits T cell responses to a superantigen. Biochemistry 40:4222–4228.
23. Li, H.,, A. Llera,, E. L. Malchiodi, and, R. A. Mariuzza. 1999. The structural basis of T cell activation by superantigens. Annu. Rev. Immunol. 17: 435466.
24. Lundberg, K.,, S. Nijenhuis,, E. R. Vossenaar,, K. Palmblad,, W. J. van Venrooij,, L. Klareskog,, A. J. Zendman, and, H. E. Harris. 2005. Citrullinated proteins have increased immunogenicity and arthritogenic–ity and their presence in arthritic joints correlates with disease severity. Arthritis Res. Ther. 7: R458R467.
25. McCormick, J. K.,, J. M. Yarwood, and, P. M. Schlievert. 2001. Toxic shock syndrome and bacterial super–antigens: an update. Annu. Rev. Microbiol. 55: 77104.
26. Nilsson, I. M.,, M. Verdrengh,, R. G. Ulrich,, S. Bavari, and, A. Tarkowski. 1999. Protection against Staphy–lococcus aureus sepsis by vaccination with recombinant staphylococcal enterotoxin A devoid of superantigenicity. J. Infect. Dis. 180: 13701373.
27. Novick, R. P.,, H. F. Ross,, S. J. Projan,, J. Kornblum,, B. Kreiswirth, and, S. Moghazeh. 1993. Synthesis of staphylococcal virulence factors is controlled by regulatory RNA molecule. EMBO J. 12: 39673975.
28. Omata, S.,, T. Sasaki,, K. Kakimoto, and, U. Yamashita. 1997. Staphylococcal enterotoxin B induces arthritis in female DBA/1 mice but fails to induce activation of type II collagen–reactive lymphocytes. Cell. Immunol. 179: 138145.
29. Palmqvist, N.,, T. J. Foster,, A. Tarkowski, and, E. Josefsson. 2002. Protein A is a virulence factor in Staphy–lococcus aureus arthritis and septic death. Microb. Pathog. 33: 239249.
30. Palmqvist, N.,, G. J. Silverman,, E. Josefsson, and, A. Tarkowski. 2005. Bacterial cell wall–expressed protein A triggers supraclonal B–cell responses upon in vivo infection with Staphylococcus aureus. Microbes Infect. 7: 15011511.
31. Reinhart, K., and, W. Karzai. 2001. Anti–tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned. Crit. Care Med. 29: S121S125.
32. Riedemann, N. C.,, R. F. Guo, and, P. A. Ward. 2003. Novel strategies for the treatment of sepsis. Nat. Med. 9: 517524.
33. Saha, B.,, B. Jaklic,, D. M. Harlan,, G. S. Gray,, C. H. June, and, R. Abe. 1996. Toxic shock syndrome toxin–1–induced death is prevented by CTLA4Ig. J. Immunol. 157: 38693875.
34. Sakiniene, E.,, T. Bremell, and, A. Tarkowski. 1996. Addition of corticosteroids to antibiotic treatment ameliorates the course of experimental Staphylococcus aureus arthritis. Arthritis Rheum. 39: 15961605.
35. Schiffenbauer, J.,, H. M. Johnson,, E. J. Butfiloski,, L. Wegrzyn, and, J. M. Soos. 1993. Staphylococcal en–terotoxins can reactivate experimental allergic encephalomyelitis. Proc. Natl. Acad. Sci. USA 90: 85438546.
36. Schiffenbauer, J.,, J. M. Soos, and, H. M. Johnson. 1998. The possible role of bacterial superantigens in the pathogenesis of autoimmune disorders. Immunol. Today 19: 117120.
37. Schwab, J. H.,, R. R. Brown,, S. K. Anderle, and, P. M. Schlievert. 1993. Superantigen can reactivate bacterial cell wall–induced arthritis. J. Immunol. 150: 41514159.
38. Soos, J. M.,, M. G. Mujtaba,, J. Schiffenbauer,, B. A. Torres, and, H. M. Johnson. 2002. Intramolecular epitope spreading induced by staphylococcal enterotoxin superantigen reactivation of experimental allergic encephalomyelitis. J. Neuroimmunol. 123: 3034.
39. Soos, J. M.,, J. Schiffenbauer, and, H. M. Johnson. 1993. Treatment of PL/J mice with the superantigen, staphylococcal enterotoxin B, prevents development of experimental allergic encephalomyelitis. J. Neuroimmunol. 43: 3943.
40. Tarkowski, A.,, M. Bokarewa,, L. V. Collins,, I. Gjertsson,, O. H. Hultgren,, T. Jin,, I. M. Jonsson,, E. Josefsson,, E. Sakiniene, and, M. Verdrengh. 2002. Current status of pathogenetic mechanisms in staphylococcal arthritis. FEMS Microbiol. Lett. 217: 125132.
41. Visvanathan, K.,, A. Charles,, J. Bannan,, P. Pugach,, K. Kashfi, and, J. B. Zabriskie. 2001. Inhibition of bacterial superantigens by peptides and antibodies. Infect. Immun. 69: 875884.
42. Yamamoto, T.,, M. Matsuuchi,, I. Katayama, and, K. Nishioka. 1998. Repeated subcutaneous injection of staphylococcal enterotoxin B–stimulated lymphocytes retains epidermal thickness of psoriatic skin–graft onto severe combined immunodeficient mice. J. Dermatol. Sci. 17: 814.
43. Zimbelman, J.,, A. Palmer, and, J. Todd. 1999. Improved outcome of clindamycin compared with beta–lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr. Infect. Dis. J. 18: 10961100.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error