Advertisement

Journal of Neuroimmune Pharmacology

, Volume 5, Issue 2, pp 168–175 | Cite as

Studies in the Modulation of Experimental Autoimmune Encephalomyelitis

  • Jane E. Libbey
  • Ikuo Tsunoda
  • Robert S. Fujinami
INVITED REVIEW

Abstract

Experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis, can be induced through inoculation with several different central nervous system (CNS) proteins or peptides. Modulation of EAE, resulting in either protection from EAE or enhancement of EAE, can also be accomplished through either vaccination or DNA immunization with molecular mimics of self-CNS proteins. Previously published data on this method of EAE modulation will be reviewed. New data is presented, which demonstrates that EAE can also be modulated through the administration of the β-(1,3)-d-glucan, curdlan. Dendritic cells stimulated by curdlan are involved in the differentiation of the interleukin-17 producing subset of CD4+ T cells that are recognized effector cells in EAE. Using two different systems to study the effects of curdlan on EAE, it was found that curdlan increased the incidence of EAE and/or the severity of the disease course.

Keywords

myelin basic protein myelin proteolipid protein myelin oligodendrocyte glycoprotein vaccination DNA immunization interleukin-17 

Notes

Acknowledgment

We wish to thank Nikki J. Kirkman, BS, Faris Hasanovic, BS, Daniel J. Doty, and Krystal D. Porter, BS, for the excellent technical assistance. We wish to acknowledge Kathleen Borick for the outstanding preparation of the manuscript.

References

  1. Amor S, Groome N, Linington C, Morris MM, Dornmair K, Gardinier MV, Matthieu J-M, Baker D (1994) Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice. J Immunol 153:4349–4356PubMedGoogle Scholar
  2. Aranami T, Yamamura T (2008) Th17 Cells and autoimmune encephalomyelitis (EAE/MS). Allergol Int 57:115–120PubMedCrossRefGoogle Scholar
  3. Barnett LA, Whitton JL, Wada Y, Fujinami RS (1993) Enhancement of autoimmune disease using recombinant vaccinia virus encoding myelin proteolipid protein [published erratum appears in J Neuroimmunol 48:120, 1993]. J Neuroimmunol 44:15–25PubMedCrossRefGoogle Scholar
  4. Barnett LA, Whitton JL, Wang LY, Fujinami RS (1996) Virus encoding an encephalitogenic peptide protects mice from experimental allergic encephalomyelitis. J Neuroimmunol 64:163–173PubMedCrossRefGoogle Scholar
  5. Fritz RB, McFarlin DE (1989) Encephalitogenic epitopes of myelin basic protein. Chem Immunol 46:101–125PubMedCrossRefGoogle Scholar
  6. Fujinami RS (2001) Can virus infections trigger autoimmune disease? J Autoimmun 16:229–234PubMedCrossRefGoogle Scholar
  7. Garren H, Ruiz PJ, Watkins TA, Fontoura P, Nguyen L-VT, Estline ER, Hirschberg DL, Steinman L (2001) Combination of gene delivery and DNA vaccination to protect from and reverse Th1 autoimmune disease via deviation to the Th2 pathway. Immunity 15:15–22PubMedCrossRefGoogle Scholar
  8. Goverman J, Perchellet A, Huseby ES (2005) The role of CD8+ T cells in multiple sclerosis and its animal models. Curr Drug Targets Inflamm Allergy 4:239–245PubMedCrossRefGoogle Scholar
  9. Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SCM, Geijtenbeek TBH (2009) Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-κB activation through Raf-1 and Syk. Nat Immunol 10:203–213PubMedCrossRefGoogle Scholar
  10. Hofstetter HH, Toyka KV, Tary-Lehmann M, Lehmann PV (2007) Kinetics and organ distribution of IL-17-producing CD4 cells in proteolipid protein 139-151 peptide-induced experimental autoimmune encephalomyelitis of SJL mice. J Immunol 178:1372–1378PubMedGoogle Scholar
  11. Huseby ES, Liggitt D, Brabb T, Schnabel B, Öhlén C, Goverman J (2001) A pathogenic role for myelin-specific CD8+ T cells in a model for multiple sclerosis. J Exp Med 194:669–676PubMedCrossRefGoogle Scholar
  12. Iezzi G, Sonderegger I, Ampenberger F, Schmitz N, Marsland BJ, Kopf M (2009) CD40-CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4+ T cells. Proc Natl Acad Sci USA 106:876–881PubMedCrossRefGoogle Scholar
  13. Ji Q, Goverman J (2007) Experimental autoimmune encephalomyelitis mediated by CD8+ T cells. Ann N Y Acad Sci 1103:157–166PubMedCrossRefGoogle Scholar
  14. Johnson AJ, Suidan GL, McDole J, Pirko I (2007) The CD8 T cell in multiple sclerosis: suppressor cell or mediator of neuropathology? Int Rev Neurobiol 79:73–97PubMedCrossRefGoogle Scholar
  15. Kim S-K, Cornberg M, Wang XZ, Chen HD, Selin LK, Welsh RM (2005) Private specificities of CD8 T cell responses control patterns of heterologous immunity. J Exp Med 201:523–533PubMedCrossRefGoogle Scholar
  16. Klemann C, Je Raveney B, Oki S, Yamamura T (2009) Retinoid signals and Th17-mediated pathology. Jpn J Clin Immunol 32:20–28CrossRefGoogle Scholar
  17. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240PubMedCrossRefGoogle Scholar
  18. Laroche C, Michaud P (2007) New developments and prospective applications for β (1, 3) glucans. Recent Pat Biotechnol 1:59–73PubMedCrossRefGoogle Scholar
  19. LeibundGut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, Schweighoffer E, Tybulewicz V, Brown GD, Ruland J, Reis e Sousa C (2007) Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 8:630–638PubMedCrossRefGoogle Scholar
  20. Libbey JE, Fujinami RS (2009) Potential triggers of MS. In: Martin R, Lutterotti A (eds) Molecular Basis of Multiple Sclerosis. The Immune System. Series: Results and Problems in Cell Differentiation. Springer, Berlin, epub January 8, 2009.Google Scholar
  21. McCoy L, Tsunoda I, Fujinami RS (2006) Multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation. Autoimmunity 39:9–19PubMedCrossRefGoogle Scholar
  22. McIntosh M, Stone BA, Stanisich VA (2005) Curdlan and other bacterial (1→3)-β-D-glucans. Appl Microbiol Biotechnol 68:163–173PubMedCrossRefGoogle Scholar
  23. Rodriguez M (2007) Effectors of demyelination and remyelination in the CNS: implications for multiple sclerosis. Brain Pathol 17:219–229PubMedCrossRefGoogle Scholar
  24. Ruiz PJ, Garren H, Ruiz IU, Hirschberg DL, Nguyen L-VT, Karpuj MV, Cooper MT, Mitchell DJ, Fathman CG, Steinman L (1999) Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: modulation of T cell costimulation. J Immunol 162:3336–3341PubMedGoogle Scholar
  25. Ruland J (2008) CARD9 signaling in the innate immune response. Ann N Y Acad Sci 1143:35–44PubMedCrossRefGoogle Scholar
  26. Sedzik J (2008) Myelin sheaths and autoimmune response induced by myelin proteins and alphaviruses. I Physicochemical background. Curr Med Chem 15:1899–1910PubMedCrossRefGoogle Scholar
  27. Selin LK, Cornberg M, Brehm MA, Kim SK, Calcagno C, Ghersi D, Puzone R, Celada F, Welsh RM (2004) CD8 memory T cells: cross-reactivity and heterologous immunity. Semin Immunol 16:335–347PubMedCrossRefGoogle Scholar
  28. Selin LK, Brehm MA, Naumov YN, Cornberg M, Kim S-K, Clute SC, Welsh RM (2006) Memory of mice and men: CD8+ T-cell cross-reactivity and heterologous immunity. Immunol Rev 211:164–181PubMedCrossRefGoogle Scholar
  29. Sobel RA, Greer JM, Kuchroo VK (1994) Minireview: autoimmune responses to myelin proteolipid protein. Neurochem Res 19:915–921PubMedCrossRefGoogle Scholar
  30. Sun D, Whitaker JN, Huang Z, Liu D, Coleclough C, Wekerle H, Raine CS (2001) Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL/6 mice. J Immunol 166:7579–7587PubMedGoogle Scholar
  31. Theil DJ, Libbey JE, Rodriguez F, Whitton JL, Tsunoda I, Derfuss TJ, Fujinami RS (2008) Targeting myelin proteolipid protein to the MHC class I pathway by ubiquitination modulates the course of experimental autoimmune encephalomyelitis. J Neuroimmunol 204:92–100PubMedCrossRefGoogle Scholar
  32. Theil DJ, Tsunoda I, Rodriguez F, Whitton JL, Fujinami RS (2001) Viruses can silently prime for and trigger central nervous system autoimmune disease. J NeuroVirol 7:220–227PubMedCrossRefGoogle Scholar
  33. Tsunoda I, Fujinami RS (1996) Two models for multiple sclerosis: experimental allergic encephalomyelitis and Theiler’s murine encephalomyelitis virus. J Neuropathol Exp Neurol 55:673–686PubMedCrossRefGoogle Scholar
  34. Tsunoda I, Kuang L-Q, Tolley ND, Whitton JL, Fujinami RS (1998) Enhancement of experimental allergic encephalomyelitis (EAE) by DNA immunization with myelin proteolipid protein (PLP) plasmid DNA. J Neuropathol Exp Neurol 57:758–767PubMedCrossRefGoogle Scholar
  35. Tsunoda I, Libbey JE, Fujinami RS (2007) Sequential polymicrobial infections lead to CNS inflammatory disease: possible involvement of bystander activation in heterologous immunity. J Neuroimmunol 188:22–33PubMedCrossRefGoogle Scholar
  36. Tuohy VK (1994) Peptide determinants of myelin proteolipid protein (PLP) in autoimmune demyelinating disease: a review. Neurochem Res 19:935–944PubMedCrossRefGoogle Scholar
  37. Veldhoen M, Hocking RJ, Flavell RA, Stockinger B (2006) Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 7:1151–1156PubMedCrossRefGoogle Scholar
  38. Wang L-Y, Fujinami RS (1997) Enhancement of EAE and induction of autoantibodies to T-cell epitopes in mice infected with a recombinant vaccinia virus encoding myelin proteolipid protein. J Neuroimmunol 75:75–83PubMedCrossRefGoogle Scholar
  39. Wang L-Y, Theil DJ, Whitton JL, Fujinami RS (1999) Infection with a recombinant vaccinia virus encoding myelin proteolipid protein causes suppression of chronic relapsing-remitting experimental allergic encephalomyelitis. J Neuroimmunol 96:148–157PubMedCrossRefGoogle Scholar
  40. Welsh RM, Kim SK, Cornberg M, Clute SC, Selin LK, Naumov YN (2006) The privacy of T cell memory to viruses. Curr Top Microbiol Immunol 311:117–153PubMedCrossRefGoogle Scholar
  41. Whitton JL, Fujinami RS (1999) Viruses as triggers of autoimmunity: facts and fantasies. Curr Opin Microbiol 2:392–397PubMedCrossRefGoogle Scholar
  42. Xie L, Li X-K, Funeshima-Fuji N, Kimura H, Matsumoto Y, Isaka Y, Takahara S (2009) Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production. Int Immunopharmacol 9:575–581PubMedCrossRefGoogle Scholar
  43. Yoshitomi H, Sakaguchi N, Kobayashi K, Brown GD, Tagami T, Sakihama T, Hirota K, Tanaka S, Nomura T, Miki I, Gordon S, Akira S, Nakamura T, Sakaguchi S (2005) A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice. J Exp Med 201:949–960PubMedCrossRefGoogle Scholar
  44. Zamvil SS, Mitchell DJ, Moore AC, Kitamura K, Steinman L, Rothbard JB (1986) T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature 324:258–260PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jane E. Libbey
    • 1
  • Ikuo Tsunoda
    • 2
  • Robert S. Fujinami
    • 1
  1. 1.Department of PathologyUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Department of Microbiology and ImmunologyLouisiana State University Health Sciences CenterShreveportUSA

Personalised recommendations