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Multiple sclerosis: a complicated picture of autoimmunity

Nature Immunology volume 8, pages 913–919 (2007)Cite this article

Abstract

Understanding of autoimmune diseases, including multiple sclerosis, has expanded considerably in recent years. New insights have been provided by not only animal models but also studies of patients, often in conjunction with experimental therapies. It is accepted that autoimmune T cells mediate the early steps of new multiple sclerosis lesions, and although uncertainties remain about the specific targets of autoreactive T cells, several studies indicate myelin antigens. Recent findings obtained with both animal models and patients with multiple sclerosis indicate involvement of a T helper cell with a TH-17 phenotype, in contrast to previous data indicating that T helper type 1 cells are critical. Evidence has also been presented for CD8+ and regulatory T cell populations, although their involvement remains to be established. Despite evidence supporting the idea that autoreactive T cells are involved in disease induction, cells of myeloid lineage, antibodies and complement as well as processes intrinsic to the central nervous system seem to determine the effector stages of tissue damage. Careful analysis of the alterations in immune processes should further advance knowledge of the relationship between the inflammatory component of this disease and the more diffuse degeneration of progressive multiple sclerosis.

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Figure 1: Immune cell populations activated in the peripheral immune system by antigen presentation by mature DCs.
Figure 2: Immunological processes during early steps in the development of multiple sclerosis lesions.
Figure 3: Effector mechanisms that lead to CNS tissue destruction.

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References

  1. Stone, L.A. et al. Blood-brain barrier disruption on contrast-enhanced MRI in patients with mild relapsing-remitting multiple sclerosis: relationship to course, gender, and age. Neurology 45, 1122–1126 (1995).

    Article  CAS  PubMed  Google Scholar 

  2. Coles, A.J. et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann. Neurol. 46, 296–304 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Hartung, H.P. et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 360, 2018–2025 (2002).

    Article  PubMed  Google Scholar 

  4. Oksenberg, J.R. & Hauser, S.L. Genetics of multiple sclerosis. Neurol. Clin. 23, 61–75 (2005).

    Article  PubMed  Google Scholar 

  5. McKenzie, B.S., Kastelein, R.A. & Cua, D.J. Understanding the IL-23-IL-17 immune pathway. Trends Immunol. 27, 17–23 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Iwakura, Y. & Ishigame, H. The IL-23/IL-17 axis in inflammation. J. Clin. Invest. 116, 1218–1222 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Brok, H.P. et al. Prevention of experimental autoimmune encephalomyelitis in common marmosets using an anti-IL-12p40 monoclonal antibody. J. Immunol. 169, 6554–6563 (2002).

    Article  CAS  PubMed  Google Scholar 

  8. Cua, D.J. et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421, 744–748 (2003).

    Article  CAS  PubMed  Google Scholar 

  9. Veldhoen, M., Hocking, R.J., Atkins, C.J., Locksley, R.M. & Stockinger, B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179–189 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Gijbels, K., Brocke, S., Abrams, J.S. & Steinman, L. Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in central nervous system and circulation. Mol. Med. 1, 795–805 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Korn, T. et al. IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 448, 484–487 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nurieva, R. et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448, 480–483 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. Wilson, N.J. et al. Development, cytokine profile and function of human interleukin 17–producing helper T cells. Nat. Immunol. 8, 950–957 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Acosta-Rodriguez, E.V. et al. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17–producing human T helper cells Nat. Immunol. 8, 942–949 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Ivanov, I.I. et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121–1133 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Liao, J.J., Huang, M.C. & Goetzl, E.J. Cutting edge: alternative signaling of TH17 cell development by sphingosine 1-phosphate. J. Immunol. 178, 5425–5428 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Kappos, L. et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N. Engl. J. Med. 355, 1124–1140 (2006).

    Article  CAS  PubMed  Google Scholar 

  18. Matusevicius, D. et al. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult. Scler. 5, 101–104 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Lock, C. et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 8, 500–508 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Vaknin-Dembinsky, A., Balashov, K. & Weiner, H.L. IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production. J. Immunol. 176, 7768–7774 (2006).

    Article  CAS  PubMed  Google Scholar 

  21. Li, Y. et al. Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia. Brain 130, 490–501 (2007).

    Article  PubMed  Google Scholar 

  22. Traugott, U., Reinherz, E.L. & Raine, C.S. Multiple sclerosis: distribution of T cell subsets within active chronic lesions. Science 219, 308–310 (1983).

    Article  CAS  PubMed  Google Scholar 

  23. Crawford, M.P. et al. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay. Blood 103, 4222–4231 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Babbe, H. et al. Clonal expansions of CD8+ T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J. Exp. Med. 192, 393–404 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ji, Q. & Goverman, J. Experimental autoimmune encephalomyelitis mediated by CD8+ T cells. Ann. NY Acad. Sci. 2203, 157–166 (2007).

    Article  CAS  Google Scholar 

  26. Brisebois, M., Zehntner, S.P., Estrada, J., Owens, T. & Fournier, S. A pathogenic role for CD8+ T cells in a spontaneous model of demyelinating disease. J. Immunol. 177, 2403–2411 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Medana, I., Martinic, M.A., Wekerle, H. & Neumann, H. Transection of major histocompatibility complex class I-induced neurites by cytotoxic T lymphocytes. Am. J. Pathol. 159, 809–815 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Coles, A.J. & Compston, A. Efficiency of alemtuzumab in treatment-naive relapsing remiting multiple sclerosis: analysis after two years of study. Neurology 68, A100 (2007).

    Google Scholar 

  29. Saccardi, R. et al. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult. Scler. 12, 814–823 (2006).

    Article  CAS  PubMed  Google Scholar 

  30. Muraro, P.A. et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J. Exp. Med. 201, 805–816 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bailey, S.L., Schreiner, B. & McMahon, E.J. CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ TH-17 cells in relapsing EAE. Nat. Immunol. 8, 172–180 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Bailey, S.L., Schreiner, B., McMahon, E.J. & Miller, S.D. CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ TH-17 cells in relapsing EAE. Nat. Immunol. 8, 172–180 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Hauser, S.L. et al. A phase II randomized, placebo-controlled trial of rituximab in adult with relapsing remitting multiple sclerosis. Neurology 68, A99 (2007).

    Article  CAS  Google Scholar 

  34. Sospedra, M. & Martin, R. Immunology of multiple sclerosis. Annu. Rev. Immunol. 23, 683–747 (2005).

    Article  CAS  PubMed  Google Scholar 

  35. Bielekova, B. et al. Expansion and functional relevance of high-avidity myelin-specific CD4+ T cells in multiple sclerosis. J. Immunol. 172, 3893–3904 (2004).

    Article  CAS  PubMed  Google Scholar 

  36. Bielekova, B. et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat. Med. 6, 1167–1175 (2000).

    Article  CAS  PubMed  Google Scholar 

  37. Muraro, P.A. et al. Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders. Brain 126, 20–31 (2003).

    Article  PubMed  Google Scholar 

  38. Fujinami, R.S., von Herrath, M.G., Christen, U. & Whitton, J.L. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin. Microbiol. Rev. 19, 80–94 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Marshak-Rothstein, A. & Rifkin, I.R. Immunologically active autoantigens: the role of toll-like receptors in the development of chronic inflammatory disease. Annu. Rev. Immunol. 25, 419–441 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Madsen, L.S. et al. A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat. Genet. 23, 343–347 (1999).

    Article  CAS  PubMed  Google Scholar 

  41. Ellmerich, S. et al. High incidence of spontaneous disease in an HLA-DR15 and TCR transgenic multiple sclerosis model. J. Immunol. 174, 1938–1946 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Ito, K. et al. HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis. J. Exp. Med. 183, 2635–2644 (1996).

    Article  CAS  PubMed  Google Scholar 

  43. Huh, J. et al. Limited repertoire of HLA-DRB1*0401-restricted MBP111–129-specific T cells in HLA-DRB1*0401 Tg mice and their pathogenic potential. J. Neuroimmunol. 151, 94–102 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Quandt, J.A. et al. Unique clinical and pathological features in HLA-DRB1*0401-restricted MBP 111–129-specific humanized TCR transgenic mice. J. Exp. Med. 200, 223–234 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ousman, S.S. et al. Protective and therapeutic role for αB-crystallin in autoimmune demyelination. Nature 48, 474–479 (2007).

    Article  CAS  Google Scholar 

  46. Vanderlugt, C.L. et al. Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis. J. Immunol. 164, 670–678 (2000).

    Article  CAS  PubMed  Google Scholar 

  47. McRae, B.L., Vanderlugt, C.L., Dal Canto, M.C. & Miller, S.D. Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J. Exp. Med. 182, 75–85 (1995).

    Article  CAS  PubMed  Google Scholar 

  48. Filippi, M. et al. Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis. Neurology 44, 635–641 (1994).

    Article  CAS  PubMed  Google Scholar 

  49. Ho, P.P. et al. A suppressive oligodeoxynucleotide enhances the efficacy of myelin cocktail/IL-4-tolerizing DNA vaccination and treats autoimmune disease. J. Immunol. 175, 6226–6234 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Stone, L.A. et al. The effect of interferon-β on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis. Ann. Neurol. 37, 611–619 (1995).

    Article  CAS  PubMed  Google Scholar 

  51. Li, D.K., Zhao, G.J. & Paty, D.W. Randomized controlled trial of interferon-β-1a in secondary progressive MS: MRI results. Neurology 56, 1505–1513 (2001).

    Article  CAS  PubMed  Google Scholar 

  52. Calabresi, P.A. et al. Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon β-1b. Ann. Neurol. 41, 669–674 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Polman, C.H. et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 354, 899–910 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Stuve, O. et al. Interferon β-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9. Ann. Neurol. 40, 853–863 (1996).

    Article  CAS  PubMed  Google Scholar 

  55. Avolio, C. et al. Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-β-1a treatment. Mult. Scler. 11, 441–446 (2005).

    Article  CAS  PubMed  Google Scholar 

  56. Argaw, A.T. et al. IL-1β regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program. J. Immunol. 177, 5574–5584 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Farina, C. et al. Preferential expression and function of Toll-like receptor 3 in human astrocytes. J. Neuroimmunol. 159, 12–19 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Kohm, A.P., Carpentier, P.A., Anger, H.A. & Miller, S.D. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 169, 4712–4716 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. Cabbage, S.E. et al. Regulatory T cells maintain long-term tolerance to myelin basic protein by inducing a novel, dynamic state of T cell tolerance. J. Immunol. 178, 887–896 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Walker, M.R. et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25− T cells. J. Clin. Invest. 112, 1437–1443 (2003).

    Article  CAS  PubMed  Google Scholar 

  61. von Boehmer, H. Mechanisms of suppression by suppressor T cells. Nat. Immunol. 6, 338–344 (2005).

    Article  CAS  PubMed  Google Scholar 

  62. Korn, T. et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 13, 423–431 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bielekova, B. et al. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon β. Proc. Natl. Acad. Sci. USA 101, 8705–8708 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kreijveld, E., Koenen, H.J., Klasen, I.S., Hilbrands, L.B. & Joosten, I. Following anti-CD25 treatment, a functional CD4+CD25+ regulatory T-cell pool is present in renal transplant recipients. Am. J. Transplant. 7, 249–255 (2007).

    Article  CAS  PubMed  Google Scholar 

  65. Bielekova, B. et al. Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis. Proc. Natl. Acad. Sci. USA 103, 5941–5946 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Julia, E. et al. Deficient Fas expression by CD4+CCR5+ T cells in multiple sclerosis. J. Neuroimmunol. 180, 147–158 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Tennakoon, D.K. et al. Therapeutic induction of regulatory, cytotoxic CD8+ T cells in multiple sclerosis. J. Immunol. 176, 7119–7129 (2006).

    Article  CAS  PubMed  Google Scholar 

  68. Hur, E.M. et al. Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat. Immunol. 8, 74–83 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. Chabas, D. et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294, 1731–1735 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Meller, R. et al. Neuroprotection by osteopontin in stroke. J. Cereb. Blood Flow Metab. 25, 217–225 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Platten, M. et al. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 310, 850–855 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Sakurai, K., Zou, J.P., Tschetter, J.R., Ward, J.M. & Shearer, G.M. Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 129, 186–196 (2002).

    Article  CAS  PubMed  Google Scholar 

  73. Vollmer, T. et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363, 1607–1608 (2004).

    Article  CAS  PubMed  Google Scholar 

  74. Youssef, S. et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420, 78–84 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. van Walderveen, M.A. et al. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology 50, 1282–1288 (1998).

    Article  CAS  PubMed  Google Scholar 

  76. Bagnato, F. et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain 126, 1782–1789 (2003).

    Article  PubMed  Google Scholar 

  77. Rebenko-Moll, N.M., Liu, L., Cardona, A. & Ransohoff, R.M. Chemokines, mononuclear cells and the nervous system: heaven (or hell) is in the details. Curr. Opin. Immunol. 18, 683–689 (2006).

    Article  CAS  PubMed  Google Scholar 

  78. Furtado, G.C. et al. A novel model of demyelinating encephalomyelitis induced by monocytes and dendritic cells. J. Immunol. 177, 6871–6879 (2006).

    Article  CAS  PubMed  Google Scholar 

  79. Lucchinetti, C. et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47, 707–717 (2000).

    Article  CAS  PubMed  Google Scholar 

  80. Magliozzi, R. et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130, 1089–1104 (2007).

    Article  PubMed  Google Scholar 

  81. Cepok, S. et al. Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis. J. Clin. Invest. 115, 1352–1360 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Genain, C.P. et al. Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J. Clin. Invest. 96, 2966–2974 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Berger, T. et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N. Engl. J. Med. 349, 139–145 (2003).

    Article  CAS  PubMed  Google Scholar 

  84. Kuhle, J. et al. Lack of association between antimyelin antibodies and progression to multiple sclerosis. N. Engl. J. Med. 356, 371–378 (2007).

    Article  CAS  PubMed  Google Scholar 

  85. Allen, I.V., McQuaid, S., Mirakhur, M. & Nevin, G. Pathological abnormalities in the normal-appearing white matter in multiple sclerosis. Neurol. Sci. 22, 141–144 (2001).

    Article  CAS  PubMed  Google Scholar 

  86. Ponomarev, E.D., Shriver, L.P., Maresz, K. & Dittel, B.N. Microglial cell activation and proliferation precedes the onset of CNS autoimmunity. J. Neurosci. Res. 81, 374–389 (2005).

    Article  CAS  PubMed  Google Scholar 

  87. Pitt, D., Werner, P. & Raine, C.S. Glutamate excitotoxicity in a model of multiple sclerosis. Nat. Med. 6, 67–70 (2000).

    Article  CAS  PubMed  Google Scholar 

  88. Killestein, J., Kalkers, N.F. & Polman, C.H. Glutamate inhibition in MS: the neuroprotective properties of riluzole. J. Neurol. Sci. 233, 113–115 (2005).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Supported by the Gemeinnützige Hertie Stiftung (R.M.).

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  1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Henry F McFarland

  2. Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, Center for Molecular Neurobiology Hamburg, University Medical Center Eppendorf, Hamburg, 20251, Germany

    Roland Martin

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McFarland, H., Martin, R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 8, 913–919 (2007). https://doi.org/10.1038/ni1507

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