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Ikuta F, Zimmerman HM (1976) Distribution of plaques in seventy autopsy cases of multiple sclerosis in the United States. Neurology 26:26–28
Dalton CM, Chard DT, Davies GR, Miszkiel KA, Altmann DR, Fernando K, Plant GT, Thompson AJ, Miller DH (2004) Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain 127:1101–1107
Miller DH, Thompson AJ, Filippi M (2003) Magnetic resonance studies of abnormalities in the normal appearing white matter and grey matter in multiple sclerosis. J Neurol 250:1407–1419
Raine CS (1984) Biology of disease. Analysis of autoimmune demyelination: its impact upon multiple sclerosis. Lab Invest 50:608–635
Smith ME, Sommer MA (1992) Association between cell-mediated demyelination and astrocyte stimulation. Prog Brain Res 94:411–422
Filippi M, Bozzali M, Rovaris M, Gonen O, Kesavadas C, Ghezzi A, Martinelli V, Grossman RI, Scotti G, Comi G, Falini A (2003) Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 126:433–437
Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120:393–399
De Stefano N, Guidi L, Stromillo ML, Bartolozzi ML, Federico A (2003) Imaging neuronal and axonal degeneration in multiple sclerosis. Neurol Sci 24:S283–S286
Grigoriadis N, Ben-Hur T,Karussis D, Milonas I (2004) Axonal damage in multiple sclerosis: a complex issue in a complex disease. Clin Neurol Neurosurg 106:211–217
Lee MA, Smith S, Palace J, Narayanan S, Silver N, Minicucci L, Filippi M, Miller DH, Arnold DL, Matthews PM (1999) Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis? Brain 122:1261–1270
Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717
Bruck W, Bitsch A, Kolenda H, Bruck Y, Stiefel M, Lassmann H (1997) Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol 42:783–793
Trapp BD, Ransohoff RM, Fisher E, Rudick RA (1999) Neurodegeneration in multiple sclerosis: relationship to neurological disability. Neuroscientist 5:48–57
Woodroofe MN, Bellamy AS, Feldmann M, Davison AN, Cuzner ML (1986) Immunocytochemical characterisation of the immune reaction in the central nervous system in multiple sclerosis. Possible role for microglia in lesion growth. J Neurol Sci 74:135–152
Oksenberg JR, Barcellos LF, Hauser SL (1999) Genetic aspects of multiple sclerosis. Semin Neurol 19:281–288
Sadovnick AD (2004) The multiple sclerosis trait: a disease waiting to happen? Clin Neurol Neurosurg 106:172–174
Dyment DA, Ebers GC, Sadovnick AD (2004) Genetics of multiple sclerosis. Lancet Neurol 3:104–110
Zorzon M, Zivadinov R, Nasuelli D, Dolfini P, Bosco A, Bratina A, Tommasi MA, Locatelli L, Cazzato G (2003) Risk factors of multiple sclerosis: a casecontrol study. Neurol Sci 24:242–247
Weller RO, Engelhardt B, Phillips MJ (1996) Lymphocyte targeting of the central nervous system: a review of afferent and efferent CNS-immune pathways. Brain Pathol 6:275–288
Wiendl H, Kieseier BC (2003) Disease-modifying therapies in multiple sclerosis: an update on recent and ongoing trials and future strategies. Expert Opin Investig Drugs 12:689–712
Brown KA (2001) Factors modifying the migration of lymphocytes across the blood-brain barrier. Int Immunopharmacol 1:2043–2062
Salmaggi A, Gelati M, Dufour A, Corsini E, Pagano S, Baccalini R, Ferrero E, Scabini S, Silei V, Ciusani E, De Rossi M (2002) Expression and modulation of IFN-gamma-inducible chemokines (IP-10, Mig, and I-TAC) in human brain endothelium and astrocytes: possible relevance for the immune invasion of the central nervous system and the pathogenesis of multiple sclerosis. J Interferon Cytokine Res 22:631–640
Sorensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, Qin S, Rottman J, Sellebjerg F, Strieter RM, Frederiksen JL, Ransohoff RM (1999) Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 103:807–815
Correale J, Bassani Molinas Mde L (2003) Temporal variations of adhesion molecules and matrix metalloproteinases in the course of MS. J Neuroimmunol 140:198–209
Cannella B, Raine CS (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 37:424–435
Kawai K, Kobayashi Y, Shiratori M, Sobue G, Tamatani T, Miyasaka M, Yoshikai Y (1996) Intrathecal administration of antibodies against LFA-1 and against ICAM-1 suppresses experimental allergic encephalomyelitis in rats. Cell Immunol 171:262–268
Gordon EJ, Myers KJ, Dougherty JP, Rosen H, Ron Y (1995) Both anti-CD11a (LFA-1) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol 62:153–160
Matsuda M, Tsukada N,Koh CS, Iwahashi T, Shimada K, Yanagisawa N (1994) Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in the spinal cord of rats during acute experimental allergic encephalomyelitis. Autoimmunity 19:15–22
Rose JW, Welsh CT, Hill KE, Houtchens MK, Fujinami RS, Townsend JJ (1999) Contrasting effects of anti-adhesion molecule therapy in experimental allergic encephalomyelitis and Theiler’s murine encephalomyelitis. J Neuroimmunol 97:110–118
Cannella B, Cross AH, Raine CS (1993) Anti-adhesion molecule therapy in experimental autoimmune encephalomyelitis. J Neuroimmunol 46:43–55
Welsh CT, Rose JW, Hill KE, Townsend JJ (1993) Augmentation of adoptively transferred experimental allergic encephalomyelitis by administration of a monoclonal antibody specific for LFA-1 alpha. J Neuroimmunol 43:161–167
Kieseier BC, Seifert T, Giovannoni G, Hartung HP (1999) Matrix metalloproteinases in inflammatory demyelination: targets for treatment. Neurology 53:20–25
Kieseier BC, Kiefer R, Clements JM, Miller K, Wells GM, Schweitzer T, Gearing AJ, Hartung HP (1998) Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis. Brain 121:159–166
Cuzner ML, Gveric D, Strand C, Loughlin AJ, Paemen L, Opdenakker G, Newcombe J (1996) The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: comparison of stages in lesion evolution. J Neuropathol Exp Neurol 55:1194–1204
Cossins JA, Clements JM, Ford J, Miller KM, Pigott R, Vos W, Van der Valk P, De Groot CJ (1997) Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions. Acta Neuropathol (Berl) 94:590–598
Lee MA, Palace J, Stabler G, Ford J, Gearing A, Miller K (1999) Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis.A longitudinal clinical and MRI study. Brain 122:191–197
Lindberg RL, De Groot CJ, Montagne L, Freitag P, van der Valk P, Kappos L, Leppert D (2001) The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain 124:1743–1753
Qin Y, Duquette P (2003) B-cell immunity in MS. Int MS J 10:110–120
Bitsch A, da Costa C, Bunkowski S, Weber F, Rieckmann P, Bruck W (1998) Identification of macrophage populations expressing tumor necrosis factor-alpha mRNA in acute multiple sclerosis. Acta Neuropathol (Berl) 95:373–377
Gilgun-Sherki Y, Melamed E, Offen D (2004) The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol 251:261–268
Kennel De March A, De Bouwerie M, Kolopp-Sarda MN, Faure GC, Bene MC, Bernard CC (2003) Anti-myelin oligodendrocyte glycoprotein B-cell responses in multiple sclerosis. J Neuroimmunol 135:117–125
Iglesias A, Bauer J, Litzenburger T, Schubart A, Linington C (2001) T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36:220–234
Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M (2003) Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 349:139–145
D’Souza SD, Bonetti B, Balasingam V, Cashman NR, Barker PA, Troutt AB, Raine CS,Antel JP (1996) Multiple sclerosis: Fas signaling in oligodendrocyte cell death. J Exp Med 184:2361–2370
Bitsch A, Kuhlmann T, Da Costa C, Bunkowski S, Polak T, Bruck W (2000) Tumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: correlation with demyelinating activity and oligodendrocyte pathology. Glia 29:366–375
Pouly S, Becher B, Blain M, Antel JP (2000) Interferon-gamma modulates human oligodendrocyte susceptibility to Fas-mediated apoptosis. J Neuropathol Exp Neurol 59:280–286
Bjartmar C, Trapp BD (2003) Axonal degeneration and progressive neurologic disability in multiple sclerosis. Neurotox Res 5:157–164
Bjartmar C, Wujek JR, Trapp BD (2003) Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 206:165–171
De Keyser J, Zeinstra E, Mostert J, Wilczak N (2004) Beta 2-adrenoceptor involvement in inflammatory demyelination and axonal degeneration in multiple sclerosis. Trends Pharmacol Sci 25:67–71
Werner P, Pitt D, Raine CS (2000) Glutamate excitotoxicity—a mechanism for axonal damage and oligodendrocyte death in multiple sclerosis? J Neural Transm Suppl 60:375–385
Neumann H (2003) Molecular mechanisms of axonal damage in inflammatory central nervous system diseases. Curr Opin Neurol 16:267–273
Bruck W, Stadelmann C (2003) Inflammation and degeneration in multiple sclerosis. Neurol Sci 24(Suppl 5):S265–S267
Neumann H, Medana IM, Bauer J, Lassmann H (2002) Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci 25:313–319
Nitsch R, Pohl EE, Smorodchenko A, Infante-Duarte C, Aktas O, Zipp F (2004) Direct impact of T cells on neurons revealed by two-photon microscopy in living brain tissue. J Neurosci 24:2458–2464
Ruffini F, Kennedy TE, Antel JP (2004) Inflammation and remyelination in the central nervous system: a tale of two systems. Am J Pathol 164:1519–1522
Kappos L, Duda P (2002) The Janus face of CNS-directed autoimmune response: a therapeutic challenge. Brain 125:2379–2380
Compston A, Coles A (2002) Multiple sclerosis. Lancet 359:1221–1231
Hemmer B, Archelos JJ, Hartung HP (2002) New concepts in the immunopathogenesis of multiple sclerosis. Nat Rev Neurosci 3:291–301
Steinman L, Martin R, Bernard C, Conlon P, Oksenberg JR (2002) Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy. Annu Rev Neurosci 25:491–505
Kieseier BC, Hartung HP (2003) Multiple paradigm shifts in multiple sclerosis. Curr Opin Neurol 16:247–252
Antel J, Bar-Or A (2004) Multiple sclerosis: therapy. In: Lazzarini R (ed) Myelin biology and disorders. Elsevier Academic Press, pp 791–806
PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group (1998) Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 352:1498–1504
Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA (1990) T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346:183–187
Pette M, Fujita K, Kitze B, Whitaker JN, Albert E, Kappos L, Wekerle H (1990) Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. Neurology 40:1770–1776
Wucherpfennig KW, Zhang J, Witek C, Matsui M, Modabber Y, Ota K, Hafler DA (1994) Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. J Immunol 152:5581–5592
Yan SS, Wu ZY, Zhang HP, Furtado G, Chen X, Yan SF, Schmidt AM, Brown C, Stern A, LaFaille J, Chess L, Stern DM, Jiang H (2003) Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. Nat Med 9:287–293
Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA (1994) Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 179:973–984
Lovett-Racke AE, Trotter JL, Lauber J, Perrin PJ, June CH, Racke MK (1998) Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients. A marker of activated/memory T cells. J Clin Invest 101:725–730
Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M (1999) Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5:49–55
Hohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H, Wekerle H (2000) The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. J Neuroimmunol 107:161–166
Martino G, Adorini L, Rieckmann P, Hillert J, Kallmann B, Comi G, Filippi M (2002) Inflammation in multiple sclerosis: the good, the bad, and the complex. Lancet Neurol 1:499–509
Owens T (2003) The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage. Curr Opin Neurol 16:259–265
Hohlfeld R, Wekerle H (2001) Immunological update on multiple sclerosis. Curr Opin Neurol 14:299–304
Noseworthy JH, Gold R, Hartung HP (1999) Treatment of multiple sclerosis: recent trials and future perspectives. Curr Opin Neurol 12:279–293
Martin R, Sturzebecher CS, McFarland HF (2001) Immunotherapy of multiple sclerosis: where are we? Where should we go? Nat Immunol 2:785–788
Wiendl H, Hohlfeld R (2002) Therapeutic approaches in multiple sclerosis: lessons from failed and interrupted treatment trials. BioDrugs 16:183–200
Kieseier BC, Hartung HP (2003) Current disease-modifying therapies in multiple sclerosis. Semin Neurol 23:133–146
Neuhaus O, Archelos JJ, Hartung HP (2003) Immunomodulation in multiple sclerosis: from immunosuppression to neuroprotection. Trends Pharmacol Sci 24:131–138
Bar-Or A, Oliveira EM, Anderson DE, Hafler DA (1999) Molecular pathogenesis of multiple sclerosis. J Neuroimmunol 100:252–259
Ransohoff RM (1999) Mechanisms of inflammation in MS tissue: adhesion molecules and chemokines. J Neuroimmunol 98:57–68
Becher B, Prat A, Antel JP (2000) Brainimmune connection: immuno-regulatory properties of CNS-resident cells. Glia 29:293–304
Yong VW, Power C, Forsyth P, Edwards DR (2001) Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2:502–511
The IFNB Multiple Sclerosis Study Group (1993) Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multi-center, randomized, double-blind, placebo-controlled trial. Neurology 43:655–661
The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group (1995) Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology 45:1277–1285
Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB and the Copolymer 1 Multiple Sclerosis Study Group (1995) Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. Neurology 45:1268–1276
Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Granger CV, Simon JH, Alam JJ, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munschauer 3rd FE, Priore RL, Pullicino PM, Scherokman BJ, Whitham RH, et al. and the Multiple Sclerosis Collaborative Research Group (MSCRG) (1996) Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 39:285–294
Rudick RA, Goodkin DE, Jacobs LD, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fischer JS, Granger CV, Simon JH, Alam JJ, Simonian NA, Campion MK, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munschauer FE, Priore RL, Whitham RH, et al. and the Multiple Sclerosis Collaborative Research Group (MSCRG) (1997) Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. Neurology 49:358–363
Goodin DS, Frohman EM, Garmany Jr GP, Halper J, Likosky WH, Lublin FD, Silberberg DH, Stuart WH, van den Noort S, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines (2002) Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 58:169–178
Yong VW (2002) Differential mechanisms of action of interferon-beta and glatiramer acetate in MS. Neurology 59:802–808
Yong VW, Chabot S, Stuve O, Williams G (1998) Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology 51:682–689
Genc K, Dona DL, Reder AT (1997) Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy. J Clin Invest 99:2664–2671
Teitelbaum D, Webb C, Meshorer A, Arnon R, Sela M (1972) Protection against experimental allergic encephalomyelitis. Nature 240:564–566
Teitelbaum D, Aharoni R, Arnon R, Sela M (1988) Specific inhibition of the T-cell response to myelin basic protein by the synthetic copolymer Cop 1. Proc Natl Acad Sci USA 85:9724–9728
Duda PW, Krieger JI, Schmied MC, Balentine C, Hafler DA (2000) Human and murine CD4 T cell reactivity to a complex antigen: recognition of the synthetic random polypeptide glatiramer acetate. J Immunol 165:7300–7307
Gran B, Tranquill LR, Chen M, Bielekova B, Zhou W, Dhib-Jalbut S, Martin R (2000) Mechanisms of immunomodulation by glatiramer acetate. Neurology 55:1704–1714
Dhib-Jalbut S, Chen M, Said A, Zhan M, Johnson KP, Martin R (2003) Glatiramer acetate-reactive peripheral blood mononuclear cells respond to multiple myelin antigens with a Th2-biased phenotype. J Neuroimmunol 140:163–171
Kim H, Ifergan I, Antel J, Seguin R, Duddy M, Lapierre Y, Jalili F, Bar-Or A (2004) Type-2 monocyte and microglia differentiation mediated by glatiramer acetate therapy in patients with multiple sclerosis. J Immunol 172:7144–7153
Miller A, Shapiro S, Gershtein R, Kinarty A, Rawashdeh H, Honigman S, Lahat N (1998) Treatment of multiple sclerosis with copolymer-1 (Copaxone): implicating mechanisms of Th1 to Th2/Th3 immune-deviation. J Neuroimmunol 92:113–121
Qin Y, Zhang DQ, Prat A, Pouly S, Antel J (2000) Characterization of T cell lines derived from glatiramer-acetate-treated multiple sclerosis patients. J Neuroimmunol 108:201–206
Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA (2000) Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J Clin Invest 105:967–976
Neuhaus O, Farina C, Yassouridis A, Wiendl H, Then Bergh F, Dose T, Wekerle H, Hohlfeld R (2000) Multiple sclerosis: comparison of copolymer-1-reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells. Proc Natl Acad Sci USA 97:7452–7457
Dabbert D, Rosner S, Kramer M, Scholl U, Tumani H, Mader M, Weber F (2000) Glatiramer acetate (copolymer-1)-specific, human T cell lines: cytokine profile and suppression of T cell lines reactive against myelin basic protein. Neurosci Lett 289:205–208
Farina C, Then Bergh F, Albrecht H, Meinl E, Yassouridis A, Neuhaus O, Hohlfeld R (2001) Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP-induced interleukin-4 and interferon-gamma response in blood cells. Brain 124:705–719
Ragheb S, Abramczyk S, Lisak D, Lisak R (2001) Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T-cells. Mult Scler 7:43–47
Chen M, Gran B, Costello K, Johnson K, Martin R, Dhib-Jalbut S (2001) Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS. Mult Scler 7:209–219
Farina C, Wagenpfeil S, Hohlfeld R (2002) Immunological assay for assessing the efficacy of glatiramer acetate (Copaxone) in multiple sclerosis. A pilot study. J Neurol 249:1587–1592
Neuhaus O, Farina C, Wekerle H, Hohlfeld R (2001) Mechanisms of action of glatiramer acetate in multiple sclerosis. Neurology 56:702–708
Schmied M, Duda PW, Krieger JI, Trollmo C, Hafler DA (2003) In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis. Clin Immunol 106:163–174
Weber MS, Starck M, Wagenpfeil S, Meinl E, Hohlfeld R, Farina C (2004) Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo. Brain 127(Pt 6):1370–1378
Moalem G, Gdalyahu A, Shani Y, Otten U, Lazarovici P, Cohen IR, Schwartz M (2000) Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun 15:331–345
Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R (1999) Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 189:865–870
Stadelmann C, Kerschensteiner M, Misgeld T, Bruck W, Hohlfeld R, Lassmann H (2002) BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 125:75–85
Ziemssen T, Kumpfel T, Klinkert WE, Neuhaus O, Hohlfeld R (2002) Glatiramer acetate-specific T-helper 1-and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain-derived neurotrophic factor. Brain 125:2381–2391
Aharoni R, Kayhan B, Eilam R, Sela M, Arnon R (2003) Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ. Proc Natl Acad Sci USA 100:14157–14162
Noronha A, Toscas A, Jensen MA (1993) Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J Neuroimmunol 46:145–153
Gelati M, Corsini E, Dufour A, Massa G, La Mantia L, Milanese C, Nespolo A, Salmaggi A (1999) Immunological effects of in vivo interferon-beta 1b treatment in ten patients with multiple sclerosis: a 1-year follow-up. J Neurol 246:569–573
Calabresi PA, Pelfrey CM, Tranquill LR, Maloni H, McFarland HF (1997) VLA-4 expression on peripheral blood lymphocytes is downregulated after treatment of multiple sclerosis with interferon beta. Neurology 49:1111–1116
Leppert D, Waubant E, Burk MR, Oksenberg JR, Hauser SL (1996) Interferon beta-1b inhibits gelatinase secretion and in vitro migration of human T cells: a possible mechanism for treatment efficacy in multiple sclerosis. Ann Neurol 40:846–852
Stuve O, Dooley NP, Uhm JH, Antel JP, Francis GS, Williams G, Yong VW (1996) Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9. Ann Neurol 40:853–863
Lou J, Gasche Y, Zheng L, Giroud C, Morel P, Clements J, Ythier A, Grau GE (1999) Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer. Lab Invest 79:1015–1025
Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23,with biological activities similar as well as distinct from IL-12. Immunity 13:715–725
Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748
Brombacher F, Kastelein RA, Alber G (2003) Novel IL-12 family members shed light on the orchestration of Th1 responses. Trends Immunol 24:207–212
Vandenbroeck K, Alloza I, Gadina M (2004) Inhibiting cytokines of the interleukin-12 family: recent advances and novel challenges. J Pharm Pharmacol 56:145–160
Rudick RA, Ransohoff RM, Peppler R, VanderBrug Medendorp S, Lehmann P, Alam J (1996) Interferon beta induces interleukin-10 expression: relevance to multiple sclerosis. Ann Neurol 40:618–627
Wang X, Chen M, Wandinger KP, Williams G, Dhib-Jalbut S (2000) IFN-beta-1b inhibits IL-12 production in peripheral blood mononuclear cells in an IL-10-dependent mechanism: relevance to IFN-beta-1b therapeutic effects in multiple sclerosis. J Immunol 165:548–557
Byrnes AA, McArthur JC, Karp CL (2002) Interferon-beta therapy for multiple sclerosis induces reciprocal changes in interleukin-12 and interleukin-10 production. Ann Neurol 51:165–174
Miller A, Lanir N, Shapiro S, Revel M, Honigman S, Kinarty A, Lahat N (1996) Immunoregulatory effects of interferon-beta and interacting cytokines on human vascular endothelial cells. Implications for multiple sclerosis autoimmune diseases. J Neuroimmunol 64:151–161
Hall GL, Wing MG, Compston DA, Scolding NJ (1997) Beta-interferon regulates the immunomodulatory activity of neonatal rodent microglia. J Neuroimmunol 72:11–19
Plioplys AV, Massimini N (1995) Alpha/beta interferon is a neuronal growth factor. Neuroimmunomodulation 2:31–35
Narayanan S, De Stefano N, Francis GS, Arnaoutelis R, Caramanos Z, Collins DL, Pelletier D, Arnason BGW, Antel JP, Arnold DL (2001) Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol 248:979–986
Teitelbaum D, Meshorer A, Hirshfeld T, Arnon R, Sela M (1971) Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur J Immunol 1:242–248
Chen M, Valenzuela RM, Dhib-Jalbut S (2003) Glatiramer acetate-reactive T cells produce brain-derived neurotrophic factor. J Neurol Sci 215:37–44
Chen M, Conway K, Johnson KP, Martin R, Dhib-Jalbut S (2002) Sustained immunological effects of glatiramer acetate in patients with multiple sclerosis treated for over 6 years. J Neurol Sci 201:71–77
Li Q, Milo R, Panitch H, Swoveland P, Bever Jr CT (1998) Glatiramer acetate blocks the activation of THP-1 cells by interferon-gamma. Eur J Pharmacol 342:303–310
Takahashi JL, Giuliani F, Power C, Imai Y, Yong VW (2003) Interleukin-1beta promotes oligodendrocyte death through glutamate excitotoxicity. Ann Neurol 53:588–595
Kipnis J, Yoles E, Porat Z, Cohen A, Mor F, Sela M, Cohen IR, Schwartz M (2000) T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc Natl Acad Sci USA 97:7446–7451
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Hans-Peter Hartung., Amit Bar-Or. & Yannis Zoukos. What do we know about the mechanism of action of disease-modifying treatments in MS?. J Neurol 251 (Suppl 5), v12–v29 (2004). https://doi.org/10.1007/s00415-004-1504-y
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DOI: https://doi.org/10.1007/s00415-004-1504-y