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References
Alter A., Duddy M., Hebert S. et al. (2003) Determinants of human B cell migration across brain endothelial cells. J. Immunol. 170:4497–4505.
Archelos J. J., Previtali S. C., Hartung H. P. (1999) The role of integrins in immune-mediated diseases of the nervous system. Trends Neurosci. 22:30–38.
Archelos J. J., Storch M. K., Hartung H. P. (2000) The role of B cells and autoantibodies in multiple sclerosis. Ann. Neurol. 47:694–706.
Babbe H., Roers A., Waisman A. et al. (2000) 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.
Baranzini S. E., Jeong M. C., Butunoi C. et al. (1999) B cell repertoire diversity and clonal expansion in multiple sclerosis brain lesions. J. Immunol. 163:5133–5144.
Barnett M. H., Prineas J. W. (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann. Neurol. 55:458–468.
Berger T., Rubner P., Schautzer F. et al. (2003) Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N. Engl. J. Med. 349:139–145.
Bjartmar C., Trapp B. D. (2001) Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr. Opin. Neurol. 14:271–278.
Buljevac D., van Doornum G. J., Flach H. Z. et al. (2005) Epstein-Barr virus and disease activity in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 76:1377–1381.
Cannella B., Raine C. S. (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann. Neurol. 37:424–435.
Casetta I., Granieri E. (2000) Clinical infections and multiple sclerosis: contribution from analytical epidemiology. J. Neurovirol. 6 Suppl 2:S147–S151.
Cepok S., Rosche B., Grummel V. et al. (2005a) Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis. Brain 128:1667–1676.
Cepok S., Zhou D., Srivastava R. et al. (2005b) Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis. J. Clin. Invest 115:1352–1360.
Chabas D., Baranzini S. E., Mitchell D. et al. (2001) The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294:1731–1735.
Christen U., von Herrath M. G. (2005) Infections and autoimmunity–good or bad? J. Immunol. 174:7481–7486.
Colombo M., Dono M., Gazzola P. et al. (2003) Maintenance of B lymphocyte-related clones in the cerebrospinal fluid of multiple sclerosis patients. Eur. J. Immunol. 33:3433–3438.
Colombo M., Dono M., Gazzola P. et al. (2000) Accumulation of clonally related B lymphocytes in the cerebrospinal fluid of multiple sclerosis patients. J. Immunol. 164:2782–2789.
Compston A., Coles A. (2002) Multiple sclerosis. Lancet 359:1221–1231.
Corcione A., Casazza S., Ferretti E. et al. (2004) Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. Proc. Natl. Acad. Sci. U. S. A 101:11064–11069.
Cserr H. F., Knopf P. M. (1992) Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol. Today 13:507–512.
Dandekar A. A., Wu G. F., Pewe L. et al. (2001) Axonal damage is T cell mediated and occurs concomitantly with demyelination in mice infected with a neurotropic coronavirus. J. Virol. 75:6115–6120.
De Stefano N., Matthews P. M., Fu L. et al. (1998) Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121:1469–1477.
Deluca G. C., Williams K., Evangelou N. et al. (2006) The contribution of demyelination to axonal loss in multiple sclerosis. Brain 129:1507–1516.
Dutta R., McDonough J., Yin X. et al. (2006) Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann. Neurol. 59:478–489.
Dyment D. A., Ebers G. C., Sadovnick A. D. (2004) Genetics of multiple sclerosis. Lancet Neurol. 3:104–110.
Ebers G. C., Sadovnick A. D., Risch N. J. (1995) A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 377:150–151.
Engelhardt B., Ransohoff R. M. (2005) The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 26:485–495.
Espejo C., Penkowa M., Demestre M. et al. (2005) Time-course expression of CNS inflammatory, neurodegenerative tissue repair markers and metallothioneins during experimental autoimmune encephalomyelitis. Neuroscience 132:1135–1149.
Friese M. A., Fugger L. (2005) Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain 128:1747–1763.
Fujinami R. S., Oldstone M. B. (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230:1043–1045.
Fujinami R. S., von Herrath M. G., Christen U. et al. (2006) Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol. Rev. 19:80–94.
Gay F. W., Drye T. J., Dick G. W. et al. (1997) The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion. Brain 120:1461–1483.
Gold R., Hartung H. P., Toyka K. V. (2000) Animal models for autoimmune demyelinating disorders of the nervous system. Mol. Med Today 6:88–91.
Gold R., Linington C., Lassmann H. (2006) Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 129:1953–1971.
Goverman J., Woods A., Larson L. et al. (1993) Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72:551–560.
Greter M., Heppner F. L., Lemos M. P. et al. (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat. Med. 11:328–334.
Haas J., Hug A., Viehover A. et al. (2005) Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur. J. Immunol. 35:3343–3352.
Hemmer B., Fleckenstein B. T., Vergelli M. et al. (1997) Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T cell clone. J. Exp. Med. 185:1651–1659.
Hemmer B., Kieseier B., Cepok S. et al. (2003) New immunopathologic insights into multiple sclerosis. Curr. Neurol. Neurosci. Rep. 3:246–255.
Hemmer B., Nessler S., Zhou D. et al. (2006) Immunopathogenesis and immunotherapy of multiple sclerosis. Nat Clin Pract Neurol 2:201–211.
Heppner F. L., Greter M., Marino D. et al. (2005) Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat. Med. 11:146–152.
Hickey W. F. (2001) Basic principles of immunological surveillance of the normal central nervous system. Glia 36:118–124.
Huseby E. S., Liggitt D., Brabb T. et al. (2001) A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. J. Exp. Med. 194:669–676.
Jacobsen M., Cepok S., Quak E. et al. (2002) Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients. Brain 125:538–550.
Jones T. B., Ankeny D. P., Guan Z. et al. (2004) Passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats. J. Neurosci. 24:3752–3761.
Kalled S. L. (2005) The role of BAFF in immune function and implications for autoimmunity. Immunol. Rev. 204:43–54.
Kawakami N., Nagerl U. V., Odoardi F. et al. (2005) Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion. J. Exp. Med. 201:1805–1814.
Kenealy S. J., Herrel L. A., Bradford Y. et al. (2006) Examination of seven candidate regions for multiple sclerosis: strong evidence of linkage to chromosome 1q44. Genes Immun. 7:73–76.
Kerschensteiner M., Stadelmann C., Dechant G. et al. (2003) Neurotrophic cross-talk between the nervous and immune systems: implications for neurological diseases. Ann. Neurol. 53:292–304.
Kieseier B. C., Storch M. K., Archelos J. J. et al. (1999) Effector pathways in immune mediated central nervous system demyelination. Curr. Opin. Neurol. 12:323–336.
Krumbholz M., Theil D., Derfuss T. et al. (2005) BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J. Exp. Med. 201:195–200.
Kuhlmann T., Lingfeld G., Bitsch A. et al. (2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125:2202–2212.
Lampasona V., Franciotta D., Furlan R. et al. (2004) Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects. Neurology 62:2092–2094.
Lang H. L., Jacobsen H., Ikemizu S. et al. (2002) A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat. Immunol. 3:940–943.
Langrish C. L., Chen Y., Blumenschein W. M. et al. (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201:233–240.
Lehmann P. V., Sercarz E. E., Forsthuber T. et al. (1993) Determinant spreading and the dynamics of the autoimmune T-cell repertoire. Immunol. Today 14:203–208.
Lucchinetti C., Bruck W., Parisi J. et al. (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47:707–717.
Madsen L. S., Andersson E. C., Jansson L. et al. (1999) A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat. Genet. 23:343–347.
McCoy L., Tsunoda I., Fujinami R. S. (2006) Multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation. Autoimmunity 39:9–19.
McDonald W. I., Compston A., Edan G. et al. (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. 50:121–127.
Mead R. J., Singhrao S. K., Neal J. W. et al. (2002) The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. J. Immunol. 168:458–465.
Meinl E., Krumbholz M., Hohlfeld R. (2006) B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann. Neurol. 59:880–892.
Miller S. D., Olson J. K., Croxford J. L. (2001) Multiple pathways to induction of virus-induced autoimmune demyelination: lessons from Theiler’s virus infection. J. Autoimmun. 16:219–227.
Moalem G., Leibowitz-Amit R., Yoles E. et al. (1999) Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat. Med. 5:49–55.
Moore F. G., Wolfson C. (2002) Human herpes virus 6 and multiple sclerosis. Acta Neurol. Scand. 106:63–83.
Neumann H., Cavalie A., Jenne D. E. et al. (1995) Induction of MHC class I genes in neurons. Science 269:549–552.
O’Connor K. C., Appel H., Bregoli L. et al. (2005) Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein. J. Immunol. 175:1974–1982.
Oksenberg J. R., Barcellos L. F., Cree B. A. et al. (2004) Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans. Am. J. Hum. Genet. 74:160–167.
Oksenberg J. R., Barcellos L. F., Hauser S. L. (1999) Genetic aspects of multiple sclerosis. Semin. Neurol. 19:281–288.
Oksenberg J. R., Stuart S., Begovich A. B. et al. (1990) Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients. Nature 345:344–346.
Ota K., Matsui M., Milford E. L. et al. (1990) T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346:183–187.
Park H., Li Z., Yang X. O. et al. (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6:1133–1141.
Parks W. C., Wilson C. L., Lopez-Boado Y. S. (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev. Immunol. 4:617–629.
Peterson J. W., Bo L., Mork S. et al. (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann. Neurol. 50:389–400.
Pitt D., Werner P., Raine C. S. (2000) Glutamate excitotoxicity in a model of multiple sclerosis. Nat. Med 6:67–70.
Polman C. H., Reingold S. C., Edan G. et al. (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann. Neurol. 58:840–846.
Poser C. M., Paty D. W., Scheinberg L. et al. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann. Neurol. 13:227–231.
Prinz M., Garbe F., Schmidt H. et al. (2006) Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis. J. Clin. Invest 116:456–464.
Qin Y., Duquette P., Zhang Y. et al. (1998) Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis. J. Clin. Invest 102:1045–1050.
Radbruch A., Muehlinghaus G., Luger E. O. et al. (2006) Competence and competition: the challenge of becoming a long-lived plasma cell. Nat. Rev. Immunol. 6:741–750.
Raine C. S., Cannella B., Hauser S. L. et al. (1999) Demyelination in primate autoimmune encephalomyelitis and acute multiple sclerosis lesions: a case for antigen-specific antibody mediation. Ann. Neurol. 46:144–160.
Ramakrishna C., Stohlman S. A., Atkinson R. D. et al. (2002) Mechanisms of central nervous system viral persistence: the critical role of antibody and B cells. J. Immunol. 168:1204–1211.
Richt J. A., Schmeel A., Frese K. et al. (1994) Borna disease virus-specific T cells protect against or cause immunopathological Borna disease. J. Exp. Med. 179:1467–1473.
Rivers T. M., Sprunt D. H., Berry G. P. (1933) Observations on the attempts to produce acute disseminated allergic encephalomyelitis in primates. J. Exp. Med 58:39–53.
Sawcer S., Ban M., Maranian M. et al. (2005) A high-density screen for linkage in multiple sclerosis. Am. J. Hum. Genet. 77:454–467.
Schluesener H. J., Sobel R. A., Linington C. et al. (1987) A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J. Immunol. 139:4016–4021.
Serafini B., Rosicarelli B., Magliozzi R. et al. (2006) Dendritic cells in multiple sclerosis lesions: maturation stage, myelin uptake, and interaction with proliferating T cells. J. Neuropathol. Exp. Neurol. 65:124–141.
Skulina C., Schmidt S., Dornmair K. et al. (2004) Multiple sclerosis: brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood. Proc. Natl. Acad. Sci. U. S. A 101:2428–2433.
Sospedra M., Martin R. (2005) Immunology of multiple sclerosis. Annu. Rev. Immunol. 23:683–747.
Sriram S., Steiner I. (2005) Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis. Ann. Neurol. 58:939–945.
Steinman L. (1999) Assessment of animal models for MS and demyelinating disease in the design of rational therapy. Neuron 24:511–514.
Stohlman S. A., Hinton D. R. (2001) Viral induced demyelination. Brain Pathol. 11:92–106.
Stys P. K. (2005) General mechanisms of axonal damage and its prevention. J. Neurol. Sci. 233:3–13.
Swanborg R. H., Whittum-Hudson J. A., Hudson A. P. (2002) Human herpesvirus 6 and Chlamydia pneumoniae as etiologic agents in multiple sclerosis -a critical review. Microbes. Infect. 4:1327–1333.
Teunissen C. E., Dijkstra C., Polman C. (2005) Biological markers in CSF and blood for axonal degeneration in multiple sclerosis. Lancet Neurol. 4:32–41.
Thacker E. L., Mirzaei F., Ascherio A. (2006) Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis. Ann. Neurol. 59:499–503.
Trapp B. D., Peterson J., Ransohoff R. M. et al. (1998) Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 338:278–285.
Trebst C., Ransohoff R. M. (2001) Investigating chemokines and chemokine receptors in patients with multiple sclerosis: opportunities and challenges. Arch. Neurol. 58:1975–1980.
Trip S. A., Schlottmann P. G., Jones S. J. et al. (2005) Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann. Neurol. 58:383–391.
Tsunoda I., Kuang L. Q., Kobayashi-Warren M. et al. (2005) Central nervous system pathology caused by autoreactive CD8+ T-cell clones following virus infection. J. Virol. 79:14640–14646.
Ubogu E. E., Cossoy M. B., Ransohoff R. M. (2006) The expression and function of chemokines involved in CNS inflammation. Trends Pharmacol. Sci. 27:48–55.
Uccelli A., Aloisi F., Pistoia V. (2005) Unveiling the enigma of the CNS as a B-cell fostering environment. Trends Immunol. 26:254–259.
Vanderlugt C. L., Miller S. D. (2002) Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat. Rev. Immunol. 2:85–95.
Viglietta V., Baecher-Allan C., Weiner H. L. et al. (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 199:971–979.
von Herrath M. G., Fujinami R. S., Whitton J. L. (2003) Microorganisms and autoimmunity: making the barren field fertile? Nat Rev. Microbiol. 1:151–157.
Waxman S. G. (2005) Sodium channel blockers and axonal protection in neuroinflammatory disease. Brain 128:5–6.
Waxman S. G. (2006) Ions, energy and axonal injury: towards a molecular neurology of multiple sclerosis. Trends Mol. Med 12:192–195.
Weaver C. T., Harrington L. E., Mangan P. R. et al. (2006) Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity. 24:677–688.
Wucherpfennig K. W., Strominger J. L. (1995) Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80:695–705.
Zhang J., Markovic-Plese S., Lacet B. et al. (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.
Zhang Y., Da R. R., Guo W. et al. (2005) Axon reactive B cells clonally expanded in the cerebrospinal fluid of patients with multiple sclerosis. J. Clin. Immunol. 25:254–264.
Zipp F., Aktas O. (2006) The brain as a target of inflammation: common pathways link inflammatory and neurodegenerative diseases. Trends Neurosci. 29:518–527.
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Menge, T., Hemmer, B., Nessler, S., Zhou, D., Kieseier, B.C., Hartung, HP. (2007). Immunopathogenesis of Multiple Sclerosis: Overview. In: Zhang, J. (eds) Immune Regulation and Immunotherapy in Autoimmune Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-36003-4_10
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